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Li J, Yan N, Li X, He S. Association between serum vitamin D concentration and liver fibrosis in diabetes mellitus patients: a cross-sectional study from the NHANES database. Acta Diabetol 2024; 61:1393-1402. [PMID: 38831202 DOI: 10.1007/s00592-024-02292-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2024] [Accepted: 04/14/2024] [Indexed: 06/05/2024]
Abstract
AIM Liver fibrosis (LF) is a common complication of diabetes mellitus (DM). Studies have found that vitamin D (VD), as a modifiable factor has been reported to be associated with LF. The relationship between serum VD concentration and LF in DM patients has rarely been reported. The aim of this study was to assess the association between serum VD concentration and LF in DM patients. METHODS In this cross-sectional study, data of DM patients aged ≥ 45 years were extracted from the National Health and Nutrition Examination Survey (NHANES 2017-2018). Serum VD concentration was measured by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Vibration controlled transient elastography (VCTE) was used to measure liver stiffness. Covariates included sociodemographic information, lifestyles, laboratory data, diseases history were extracted from the database. The weighted univariable and multivariable logistic regression models were utilized to explore the association between serum VD concentration and LF in DM patients, and were described as odds ratio (ORs) and 95% confidence intervals (CIs). Subgroup analyses based on BMI, liver steatosis, hypertension and dyslipidemia were further assessed the association. RESULTS A total of 799 patients were included, of which 188 (23.53%) had LF. Higher serum VD concentration was associated with the lower odds of LF (OR = 0.33, 95% CI 0.19-0.59) and advanced LF (OR = 0.31, 95% CI 0.17-0.55) in DM patients after adjustment for race, liver steatosis, BMI, smoking, drinking, AST, ALT and physical activity, especially in patients with liver steatosis (OR = 0.28, 95% CI 0.13-0.59) and dyslipidemia (OR = 0.31, 95% CI 0.14-0.66), respectively. CONCLUSIONS High serum VD concentration may have a potential benefit for maintain the liver health in DM patients.
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Affiliation(s)
- Jing Li
- Department of Endocrinology Diabetes, Shaanxi Provincial People's Hospital, No. 256 Youyi West Road, Beilin District, Xi'an, 710068, China
| | - Ni Yan
- Department of Endocrinology Diabetes, Shaanxi Provincial People's Hospital, No. 256 Youyi West Road, Beilin District, Xi'an, 710068, China
| | - Xiaofeng Li
- Department of Endocrinology Diabetes, Shaanxi Provincial People's Hospital, No. 256 Youyi West Road, Beilin District, Xi'an, 710068, China
| | - Shenglin He
- Department of Endocrinology Diabetes, Shaanxi Provincial People's Hospital, No. 256 Youyi West Road, Beilin District, Xi'an, 710068, China.
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Chen J, Qin Y, Li Z, Shan A, Ma Q. Aromatic Amino Acids Promote Lipid Metabolism Disorders by Increasing Hepatic Bile Acid Synthesis. J Nutr 2024; 154:1321-1332. [PMID: 38582699 DOI: 10.1016/j.tjnut.2023.12.047] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2023] [Revised: 12/11/2023] [Accepted: 12/27/2023] [Indexed: 04/08/2024] Open
Abstract
BACKGROUND Obesity is a progressive metabolic disease that begins with lipid metabolism disorders. Aromatic amino acids (AAAs), including tryptophan, phenylalanine, and tyrosine, have diverse biological activities as nutrients. However, the underlying mechanisms by which AAAs affect lipid metabolism are unclear. OBJECTIVES This study was designed to investigate the possible roles and underlying molecular mechanisms of AAA in the pathogenesis of lipid metabolism disorders. METHODS We added an AAA mixture to the high-fat diet (HFD) of mice. Glucose tolerance test was recorded. Protein expression of hepatic bile acid (BA) synthase and mRNA expression of BA metabolism-related genes were determined. Hepatic BA profiles and gut microbial were also determined in mice. RESULTS The results showed that AAA significantly increased body weight and white adipose tissue, aggravated liver injury, impaired glucose tolerance and intestinal integrity, and significantly increased hepatic BA synthesis by inhibiting intestinal farnesoid X receptor (FXR). Moreover, AAA increased the content of total BA in the liver and altered the hepatic BA profile, with elevated levels of lithocholic acid, glycochenodeoxycholic acid, and glycoursodeoxycholic acid. AAA markedly increased the levels of proteins involved in BA synthesis (cholesterol 7α-hydroxylase and oxysterol 7α-hydroxylase) and inhibited the intestinal FXR. Gut microbial composition also changed, reducing the abundance of some beneficial bacteria, such as Parvibacter and Lactobacillus. CONCLUSIONS Under HFD conditions, AAAs stimulate BA synthesis in both the classical and alternative pathways, leading to aggravation of liver injury and fat deposition. Excessive intake of AAA disrupts BA metabolism and contributes to the development of lipid metabolism disorders, suggesting that AAA may be a causative agent of lipid metabolism disorders.
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Affiliation(s)
- Jiayi Chen
- College of Animal Science and Technology, Northeast Agricultural University, Harbin, China
| | - Yingjie Qin
- College of Animal Science and Technology, Northeast Agricultural University, Harbin, China
| | - Zhongyu Li
- College of Animal Science and Technology, Northeast Agricultural University, Harbin, China
| | - Anshan Shan
- College of Animal Science and Technology, Northeast Agricultural University, Harbin, China
| | - Qingquan Ma
- College of Animal Science and Technology, Northeast Agricultural University, Harbin, China.
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Park Y, Smith-Warner SA, Zhang X, Park YJ, Kim H, Park H, Lee HA, Jung S. Association between use of vitamin and mineral supplement and non-alcoholic fatty liver disease in hypertensive adults. Sci Rep 2023; 13:13670. [PMID: 37608217 PMCID: PMC10444877 DOI: 10.1038/s41598-023-40868-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Accepted: 08/17/2023] [Indexed: 08/24/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common hepatic metabolic disorder in hypertensive adults. Impaired metabolism of micronutrients may increase NAFLD risk by exacerbating oxidative stress, insulin resistance, and inflammation among hypertensive adults. In this first cross-sectional analysis of 7,376 hypertensive adults with 2,015 NAFLD cases in the Korea National Health and Nutrition Examination Survey, vitamin and mineral supplements (VMS) use was identified via questionnaire. NAFLD was defined by a hepatic steatosis index > 36. Multivariable-adjusted odds ratios (MVOR) and 95% confidence intervals (CIs) were calculated using logistic regression models. In our study, 18.6% were current users of VMS; of these, 76.7% used multi-vitamin/mineral supplements. Current VMS users had significantly lower odds of NAFLD, compared with non-users (MVOR [95% CI]: 0.73 [0.58-0.92]). The inverse association became attenuated and non-significant among those consuming VMS at higher frequency (≥ 2 times/day), for longer duration (> 16 months), and taking ≥ 2 VMS products. The inverse association with current use of VMS was only evident in those aged < 56 years (MVOR [95% CI]: 0.54 [0.40-0.72]) and men (MVOR [95% CI]: 0.56 [0.40-0.80])(Pinteraction ≤ 0.04). Our results suggest that VMS use may lower NAFLD risk, particularly among younger or male hypertensive adults, if taken in moderation.
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Affiliation(s)
- Yoonmi Park
- Department of Nutritional Science and Food Management, Ewha Womans University, Seoul, 03760, Republic of Korea
- Graduate Program in System Health Science and Engineering, Ewha Womans University, Seoul, Republic of Korea
| | - Stephanie A Smith-Warner
- Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA, USA
- Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, USA
| | - Xuehong Zhang
- Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA, USA
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Yoon Jung Park
- Department of Nutritional Science and Food Management, Ewha Womans University, Seoul, 03760, Republic of Korea
- Graduate Program in System Health Science and Engineering, Ewha Womans University, Seoul, Republic of Korea
| | - Hyesook Kim
- Department of Food and Nutrition, Wonkwang University, Jeonbuk, Republic of Korea
| | - Hyesook Park
- Graduate Program in System Health Science and Engineering, Ewha Womans University, Seoul, Republic of Korea
- Department of Preventive Medicine, College of Medicine, Ewha Womans University, Seoul, Republic of Korea
| | - Hye Ah Lee
- Clinical Trial Center, Mokdong Hospital, Ewha Womans University, Seoul, Republic of Korea
| | - Seungyoun Jung
- Department of Nutritional Science and Food Management, Ewha Womans University, Seoul, 03760, Republic of Korea.
- Graduate Program in System Health Science and Engineering, Ewha Womans University, Seoul, Republic of Korea.
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San J, Hu J, Pang H, Zuo W, Su N, Guo Z, Wu G, Yang J. Taurine Protects against the Fatty Liver Hemorrhagic Syndrome in Laying Hens through the Regulation of Mitochondrial Homeostasis. Int J Mol Sci 2023; 24:10360. [PMID: 37373507 DOI: 10.3390/ijms241210360] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2023] [Revised: 06/13/2023] [Accepted: 06/17/2023] [Indexed: 06/29/2023] Open
Abstract
Metabolic-associated fatty liver disease (MAFLD) is a chronic liver disease caused by fat deposition in the liver of humans and mammals, while fatty liver hemorrhagic syndrome (FLHS) is a fatty liver disease in laying hens which can increase the mortality and cause severe economic losses to the laying industry. Increasing evidence has shown a close relationship between the occurrence of fatty liver disease and the disruption of mitochondrial homeostasis. Studies have proven that taurine can regulate hepatic fat metabolism, reduce hepatic fatty deposition, inhibit oxidative stress, and alleviate mitochondrial dysfunction. However, the mechanisms by which taurine regulates mitochondrial homeostasis in hepatocytes need to be further studied. In this study, we determined the effects and mechanisms of taurine on high-energy low-protein diet-induced FLHS in laying hens and in cultured hepatocytes in free fatty acid (FFA)-induced steatosis. The liver function, lipid metabolism, antioxidant capacity, mitochondrial function, mitochondrial dynamics, autophagy, and biosynthesis were detected. The results showed impaired liver structure and function, mitochondrial damage and dysfunction, lipid accumulation, and imbalance between mitochondrial fusion and fission, mitochondrial autophagy, and biosynthesis in both FLHS hens and steatosis hepatocytes. Taurine administration can significantly inhibit the occurrence of FLHS, protect mitochondria in hepatocytes from disease induced by lipid accumulation and FFA, up-regulate the expression levels of Mfn1, Mfn2, Opa1, LC3I, LC3II, PINK1, PGC-1α, Nrf1, Nrf2, and Tfam, and down-regulate the expression levels of Fis1, Drp1, and p62. In conclusion, taurine can protect laying hens from FLHS through the regulation of mitochondrial homeostasis, including the regulation of mitochondrial dynamics, autophagy, and biosynthesis.
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Affiliation(s)
- Jishuang San
- Liaoning Provincial Key Laboratory of Zoonosis, College of Animal Science & Veterinary Medicine, Shenyang Agricultural University, Shenyang 110866, China
| | - Jianmin Hu
- Liaoning Provincial Key Laboratory of Zoonosis, College of Animal Science & Veterinary Medicine, Shenyang Agricultural University, Shenyang 110866, China
| | - Huiping Pang
- Liaoning Provincial Key Laboratory of Zoonosis, College of Animal Science & Veterinary Medicine, Shenyang Agricultural University, Shenyang 110866, China
| | - Wenjun Zuo
- Liaoning Provincial Key Laboratory of Zoonosis, College of Animal Science & Veterinary Medicine, Shenyang Agricultural University, Shenyang 110866, China
| | - Na Su
- Liaoning Provincial Key Laboratory of Zoonosis, College of Animal Science & Veterinary Medicine, Shenyang Agricultural University, Shenyang 110866, China
| | - Zimeng Guo
- Liaoning Provincial Key Laboratory of Zoonosis, College of Animal Science & Veterinary Medicine, Shenyang Agricultural University, Shenyang 110866, China
| | - Gaofeng Wu
- Liaoning Provincial Key Laboratory of Zoonosis, College of Animal Science & Veterinary Medicine, Shenyang Agricultural University, Shenyang 110866, China
| | - Jiancheng Yang
- Liaoning Provincial Key Laboratory of Zoonosis, College of Animal Science & Veterinary Medicine, Shenyang Agricultural University, Shenyang 110866, China
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Mohamed AA, Halim AA, Mohamed S, Mahmoud SM, Bahgat Eldemiry EM, Mohamed RS, Shaheen MM, Naguib GG, Muharram NM, Khalil MG, Saed S, Ibrahim R, Salah Seif A, Kamal N, Nasraldin K, Abdelrahman AE, El Borolossy R. The effect of high oral loading dose of cholecalciferol in non-alcoholic fatty liver disease patients. A randomized placebo controlled trial. Front Pharmacol 2023; 14:1149967. [PMID: 36998617 PMCID: PMC10043211 DOI: 10.3389/fphar.2023.1149967] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2023] [Accepted: 03/02/2023] [Indexed: 03/15/2023] Open
Abstract
Background and Aim: Non-alcoholic fatty liver (NAFLD) is one of the most common progressive metabolic disorders worldwide. There are increasing scientific interests nowadays for the association between vitamin D status and Non-alcoholic fatty liver. Earlier studies have revealed that vitamin D deficiency is highly prevalent in Non-alcoholic fatty liver patients that contributes to poor outcomes. Hence, the present study aimed to assess the efficacy and safety of oral cholecalciferol on Non-alcoholic fatty liver patients.Subjects and Methods: This study was conducted on 140 patients that were randomized either to group 1 that received the standard conventional therapy in addition to placebo or group 2 that received the standard conventional therapy in addition to cholecalciferol during the 4 months study period.Results: At the end of the study group 2 revealed significant decrease (p < 0.05) in the mean serum level of TG, LDL-C, TC, hsCRP as compared to their baseline results and group 1 results. Additionally, a significant improvement in the serum levels of ALT (p = 0.001) was seen in group 2 at the end of the study when compared to group 1. Whereas group 1 did not show any change in these parameters when compared to group 2 and their baseline results.Conclusion: Cholecalciferol was shown to have beneficial effects on serum ALT levels, hsCRP levels and lipid profile of NAFLD patients.Clinical Trial Registration:https://prsinfo.clinicaltrials.gov/prs-users-guide.html, identifier NCT05613192
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Affiliation(s)
- Amal Ahmed Mohamed
- Department of Biochemistry and Molecular Biology, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt
| | - Ahmed Abdel Halim
- Tropical Medicine Department, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt
| | - Sahar Mohamed
- Tropical Medicine Department, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt
| | | | | | - Rasha Sobh Mohamed
- Internal Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | | | - Gina G. Naguib
- Department of Internal Medicine, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Nashwa M. Muharram
- Medical Biochemistry and Molecular Biology, Faculty of Medicine, Menoufia University, Menoufia, Egypt
| | - Mona G. Khalil
- Pharmacology and Toxicology Department, Faculty of Pharmacy, Modern University for Technology and Information, Cairo, Egypt
| | - Salma Saed
- Clinical and Chemical Pathology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Randa Ibrahim
- Clinical and Chemical Pathology Department, Nutrition Institute, Cairo, Egypt
| | - Ahmed Salah Seif
- Tropical Medicine Hepatology and Gastroenterology Department, Shebeen El-Kom Teaching Hospital, Menoufia, Egypt
| | - Noha Kamal
- Clinical Pathology Department, Theodor Bilharz Research Institute (TBRI), Ministry of Scientific Research and Higher Education, Gulf Medical University (GMU), Cairo, Egypt
| | - Karima Nasraldin
- Faculty of Biotechnology, Modern Science and Arts University, Cairo, Egypt
| | - Ali Elsaid Abdelrahman
- Diagnostic and Intervention Radiology, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt
| | - Radwa El Borolossy
- Department of Clinical Pharmacy, Faculty of Pharmacy Ain Shams University, Cairo, Egypt
- *Correspondence: Radwa El Borolossy,
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Yuan S, Larsson SC. Inverse Association Between Serum 25-Hydroxyvitamin D and Nonalcoholic Fatty Liver Disease. Clin Gastroenterol Hepatol 2023; 21:398-405.e4. [PMID: 35101633 DOI: 10.1016/j.cgh.2022.01.021] [Citation(s) in RCA: 23] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2021] [Revised: 01/12/2022] [Accepted: 01/17/2022] [Indexed: 01/28/2023]
Abstract
BACKGROUND & AIMS Serum 25-hydroxyvitamin D [S-25(OH)D] and nonalcoholic fatty liver disease (NAFLD) are correlated in many observational studies, whereas the causality of this association is uncertain, especially in European populations. We conducted a bidirectional Mendelian randomization study to determine the association between S-25(OH)D and NAFLD. METHODS Seven and 6 independent genetic variants associated with S-25(OH)D and NAFLD at the genome-wide-significance level, respectively, were selected as instrumental variables. Summary-level data for S-25(OH)D were obtained from the Study of Underlying Genetic Determinants of Vitamin D and Highly Related Traits consortium including 79,366 individuals. Summary-level data for NAFLD were available from a genome-wide association meta-analysis (1483 cases and 17,781 controls), the FinnGen consortium (894 cases and 217,898 controls), and the UK Biobank study (275 cases and 360,919 controls). Summary-level data for 4 liver enzymes were obtained from the UK Biobank. RESULTS There were genetic correlations of S-25(OH)D with NAFLD and certain liver enzymes. Genetically predicted higher levels of S-25(OH)D were consistently associated with a decreased risk of NAFLD in the 3 sources. For a 1-SD increase in genetically predicted S-25(OH)D levels, the combined odds ratio of NAFLD was 0.78 (95% confidence interval [CI], 0.69 to 0.89). Genetically predicted higher levels of S-25(OH)D showed a borderline association with aspartate aminotransferase levels (change -1.17; 95% CI, -1.36 to 0.01). Genetic predisposition to NAFLD was not associated with S-25(OH)D (change 0.13; 95% CI, -1.26 to 0.53). CONCLUSIONS Our findings have clinical implications as they suggest that increased vitamin D levels may play a role in NAFLD prevention in European populations.
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Affiliation(s)
- Shuai Yuan
- Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Susanna C Larsson
- Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Unit of Medical Epidemiology, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
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Sheng Q, Shi H, Liu S, Zhuang L, Zhao Z, Xin Y. Serum 25-hydroxyvitamin D levels and the risk of non-alcoholic fatty liver: A two-sample Mendelian randomization study. Saudi J Gastroenterol 2023; 29:39-46. [PMID: 36254930 PMCID: PMC10117008 DOI: 10.4103/sjg.sjg_297_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/25/2023] Open
Abstract
BACKGROUND Accumulated studies have shown that low expression of 25-hydroxyvitamin D [25(OH)D] was significantly associated with the risk of non-alcoholic fatty liver disease (NAFLD). However, the exact causality is still unknown. The aim of this study was to investigate whether levels of 25(OH)D are associated with risk of NAFLD, using a two-sample Mendelian randomization (MR). METHODS Data from a recent large vitamin D genome-wide association study (GWAS) on 417,580 Europeans were utilized, and the largest published histology-based NAFLD GWAS study (1,483 cases and 17,781 healthy controls) for genetic variants predicted to cause NAFLD were searched. All genetic datasets for the MR analyses were obtained using publicly available summary statistics based on individuals of European ancestry from the MR-Base and NHGRI-EBI GWAS Catalog database. Inverse-variance weighted (IVW) MR approach was used to estimate causal effects in the main analysis, complemented by 4 additional methods to control for pleiotropy. Sensitivity analyses were conducted to verify whether heterogeneity and pleiotropy can bias the MR results. RESULTS The MR analysis did not provide strong evidence for the causal association of circulating 25(OH)D with NAFLD by IVW method (OR = 0.746, 95%CI 0.517-1.078; P = 0.119). The results were consistent using four other MR methods. Sensitivity analysis using all different analytical approaches yielded similar results. There was no evidence for pleiotropy (MR-Egger intercept: -0.0003758, P = 0.970). The replication process also showed consistent results using IVW method (P = 0.710). CONCLUSION This study indicates that serum 25(OH)D levels did not possess an obvious effect on the risk of NAFLD. The associations in previous studies may be due to residual confounding or reverse causation.
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Affiliation(s)
- Qi Sheng
- Department of Infectious Disease, Qingdao Municipal Hospital, Cheeloo College of Medicine, Shandong University, Jinan; Department of Nutrition, The Affiliated Hospital of Qingdao University, Qingdao, Shangdong, China
| | - Huanchen Shi
- School of Basic Medicine, College of Medicine, Qingdao University, Qingdao, Shangdong, China
| | | | | | | | - Yongning Xin
- Department of Infectious Disease, Qingdao Municipal Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shangdong; Department of Infectious Disease, Qingdao Municipal Hospital, Qingdao University, Qingdao, China
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KEÇELİ BAŞARAN M, GÜRKAN O. Analysis of clinical findings and serum micronutrients in pediatric patients with nonalcoholic fatty liver disease. JOURNAL OF HEALTH SCIENCES AND MEDICINE 2023. [DOI: 10.32322/jhsm.1190206] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023] Open
Abstract
Aim: Serum micronutrient levels play an important role in liver metabolism. This study examines risk factors and diagnostic methods for patients on follow-up due to nonalcoholic fatty liver disease (NAFLD). NAFLD and the control groups were compared for clinical findings, serum ferritin, B12, and vitamin D levels, and their relationship with NAFLD was examined.
Material and Method: Included in the study were 60 NAFLD patients and 66 other children that formed the control group. The two groups were compared in serum lipid profile, aminotransferase, insulin, glucose, and HOMA-IR. Ultrasonography (USG) and Shear wave elastography (SWE) were performed on all patients. Both groups were then analyzed in terms of serum ferritin, B12, and vitamin D levels.
Results: NAFLD and control groups were compared in terms of USG and SWE results. 35% (n=21)of the patients in the NAFLD group had grade 1, 55% (n=33) had grade 2 and 10% (n=6) had grade 3 adiposity. HOMA-IR and insulin levels were higher in the NAFLD group (p=0.02; p=0.001). While the serum ferritin level of the patients in the NAFLD group was higher than the control group (p=0.001); the B12 level was lower (p=0.006). In terms of vitamin D, there was no difference (p=0.368).
Conclusion: It is essential to identify risk factors in children on follow-up due to NAFLD. USG and liver function tests remain the first option in the diagnosis and screening of NAFLD in children. Serum ferritin, B12, and vitamin D levels of children on follow-up due to NAFLD should be analyzed in consideration of liver fattening.
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Affiliation(s)
- Meryem KEÇELİ BAŞARAN
- SAĞLIK BİLİMLERİ ÜNİVERSİTESİ, İSTANBUL BAŞAKŞEHİR ÇAM VE SAKURA ŞEHİR SAĞLIK UYGULAMA VE ARAŞTIRMA MERKEZİ, DAHİLİ TIP BİLİMLERİ BÖLÜMÜ, ÇOCUK SAĞLIĞI VE HASTALIKLARI ANABİLİM DALI
| | - Okan GÜRKAN
- İSTANBUL GAZİOSMANPAŞA TAKSİM EĞİTİM VE ARAŞTIRMA HASTANESİ, RADYOLOJİ
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Du T, Xiang L, Zhang J, Yang C, Zhao W, Li J, Zhou Y, Ma L. Vitamin D improves hepatic steatosis in NAFLD via regulation of fatty acid uptake and β-oxidation. Front Endocrinol (Lausanne) 2023; 14:1138078. [PMID: 37033263 PMCID: PMC10074590 DOI: 10.3389/fendo.2023.1138078] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2023] [Accepted: 03/02/2023] [Indexed: 04/11/2023] Open
Abstract
INTRODUCTION The study aimed to explore the association of serum 25(OH)D3 and hepatic steatosis in non-alcoholic fatty liver disease (NAFLD) patients and to determine whether the effect of vitamin D (VD) is mediated by activation of the peroxisome proliferator-activated receptor α (PPARα) pathway. METHODS The study contained a case-control study, in vivo and in vitro experiments. A case-control study was conducted to compare serum parameters between NAFLD patients and controls and to evaluate the association of 25(OH)D3 and NAFLD. In vivo study, male Wistar rats were randomly divided into control and model groups, fed a standard chow diet and a high-fat diet (HFD), respectively, for 7 weeks to generate an NAFLD model. Then, the rats were treated with VD and a PPARα antagonist (MK886) for 7 weeks. Tissue and serum were collected and assessed by biochemical assays, morphological analysis, histological analysis, and western blot analysis. In vitro, HepG2 cells were incubated with oleic acid (OA) to induce steatosis, which was evaluated by staining. HepG2 cells were pretreated with MK886 followed by calcitriol treatment, and differences in lipid metabolism-related proteins were detected by western blot. RESULTS NAFLD patients were characterized by impaired liver function, dyslipidemia, and insulin resistance. Serum 25(OH)D3 was negatively associated with alanine aminotransferase (ALT) in NAFLD. VD deficiency was a risk factor for patients with no advanced fibrosis. Adequate VD status (25(OH)D3 >20 ng/mL) had a protective effect in patients after adjustment for confounding variables. NAFLD rats showed hyperlipidemia with severe hepatic steatosis, systematic inflammation, and lower serum 25(OH)D3. VD treatment ameliorated hepatic steatosis both in NAFLD rats and OA-induced HepG2 cells. Further, MK886 inhibited the anti-steatosis effect of VD. CONCLUSION The study revealed that an adequate VD level may act as a protective factor in NAFLD and that VD may alleviate hepatic steatosis via the PPARα signaling pathway.
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Affiliation(s)
- Tingwan Du
- Department of Nutrition and Food Hygiene, School of Public Health, Southwest Medical University, Luzhou, China
| | - Lian Xiang
- Department of Nutrition and Food Hygiene, School of Public Health, Southwest Medical University, Luzhou, China
| | - Jingjing Zhang
- Department of Clinical Nutrition, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Chunmei Yang
- Health Management Center, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Wenxin Zhao
- Department of Nutrition and Food Hygiene, School of Public Health, Southwest Medical University, Luzhou, China
| | - Jialu Li
- Department of Nutrition and Food Hygiene, School of Public Health, Southwest Medical University, Luzhou, China
| | - Yong Zhou
- Department of Medical Cell Biology and Genetics, School of Basic Medical Science, Southwest Medical University, Luzhou, China
- *Correspondence: Yong Zhou, ; Ling Ma,
| | - Ling Ma
- Department of Nutrition and Food Hygiene, School of Public Health, Southwest Medical University, Luzhou, China
- Environmental Health Effects and Risk Assessment Key Laboratory of Luzhou, School of Public Health, Southwest Medical University, Luzhou, China
- *Correspondence: Yong Zhou, ; Ling Ma,
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Le MH, Yeo YH, Li X, Li J, Zou B, Wu Y, Ye Q, Huang DQ, Zhao C, Zhang J, Liu C, Chang N, Xing F, Yan S, Wan ZH, Tang NSY, Mayumi M, Liu X, Liu C, Rui F, Yang H, Yang Y, Jin R, Le RHX, Xu Y, Le DM, Barnett S, Stave CD, Cheung R, Zhu Q, Nguyen MH. 2019 Global NAFLD Prevalence: A Systematic Review and Meta-analysis. Clin Gastroenterol Hepatol 2022; 20:2809-2817.e28. [PMID: 34890795 DOI: 10.1016/j.cgh.2021.12.002] [Citation(s) in RCA: 380] [Impact Index Per Article: 126.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2021] [Revised: 11/25/2021] [Accepted: 12/02/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS The increasing rates of obesity and type 2 diabetes mellitus may lead to increased prevalence of nonalcoholic fatty liver disease (NAFLD). We aimed to determine the current and recent trends on the global and regional prevalence of NAFLD. METHODS Systematic search from inception to March 26, 2020 was performed without language restrictions. Two authors independently performed screening and data extraction. We performed meta-regression to determine trends in NAFLD prevalence. RESULTS We identified 17,244 articles from literature search and included 245 eligible studies involving 5,399,254 individuals. The pooled global prevalence of NAFLD was 29.8% (95% confidence interval [CI], 28.6%-31.1%); of these, 82.5% of included articles used ultrasound to diagnose NAFLD, with prevalence of 30.6% (95% CI, 29.2%-32.0%). South America (3 studies, 5716 individuals) and North America (4 studies, 18,236 individuals) had the highest NAFLD prevalence at 35.7% (95% CI, 34.0%-37.5%) and 35.3% (95% CI, 25.4%-45.9%), respectively. From 1991 to 2019, trend analysis showed NAFLD increased from 21.9% to 37.3% (yearly increase of 0.7%, P < .0001), with South America showing the most rapid change of 2.7% per year, followed by Europe at 1.1%. CONCLUSIONS Despite regional variation, the global prevalence of NAFLD is increasing overall. Policy makers must work toward reversing the current trends by increasing awareness of NAFLD and promoting healthy lifestyle environments.
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Affiliation(s)
- Michael H Le
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California
| | - Yee Hui Yeo
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California; Division of General Internal Medicine, Cedars-Sinai Medical Center, Los Angeles, California
| | - Xiaohe Li
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California; Division of Infectious Disease, The Third People's Hospital of Shenzhen, Shenzhen, China
| | - Jie Li
- Department of Infectious Disease, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Ji'nan, Shandong, China
| | - Biyao Zou
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California; Department of Epidemiology and Population Health, Stanford University School of Medicine, Stanford, California
| | - Yuankai Wu
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California; Department of Infectious Diseases, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Qing Ye
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California; The Third Central Clinical College of Tianjin Medical University, Tianjin; Department of Hepatology of The Third Central Hospital of Tianjin; Tianjin Key Laboratory of Artificial Cells, Tianjin, China
| | - Daniel Q Huang
- Department of Medicine, Yong Loo Lin School of Medicine and Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore
| | - Changqing Zhao
- Department of Cirrhosis, Institute of Liver Disease, Shuguang Hospital, Shanghai University of T.C.M., Shanghai, China
| | - Jie Zhang
- Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Ji'nan, Shandong, China
| | - Chenxi Liu
- Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Ji'nan, Shandong, China
| | - Na Chang
- Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Ji'nan, Shandong, China
| | - Feng Xing
- Department of Cirrhosis, Institute of Liver Disease, Shuguang Hospital, Shanghai University of T.C.M., Shanghai, China
| | - Shiping Yan
- Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Ji'nan, Shandong, China
| | - Zi Hui Wan
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Natasha Sook Yee Tang
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Maeda Mayumi
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California
| | - Xinting Liu
- Medical School of Chinese People's Liberation Army, Beijing, and Department of Pediatrics, the First Medical Center, Chinese People's Liberation Army General Hospital, Beijing, China
| | - Chuanli Liu
- Department of Infectious Disease, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Ji'nan, Shandong, China
| | - Fajuan Rui
- Department of Infectious Disease, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Ji'nan, Shandong, China
| | - Hongli Yang
- Department of Infectious Disease, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Ji'nan, Shandong, China
| | - Yao Yang
- Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Ji'nan, Shandong, China
| | - Ruichun Jin
- Jining Medical University, Jining, Shandong, China
| | - Richard H X Le
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California
| | - Yayun Xu
- Department of Infectious Disease, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Ji'nan, Shandong, China
| | - David M Le
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California
| | - Scott Barnett
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California
| | | | - Ramsey Cheung
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California; Division of Gastroenterology and Hepatology, Veterans Affairs Palo Alto Health Care System, Palo Alto, California
| | - Qiang Zhu
- Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Ji'nan, Shandong, China
| | - Mindie H Nguyen
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California; Department of Epidemiology and Population Health, Stanford University School of Medicine, Stanford, California.
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Vitamin D Status and Steatohepatitis in Obese Diabetic and Non-Diabetic Patients. J Clin Med 2022; 11:jcm11185482. [PMID: 36143129 PMCID: PMC9503920 DOI: 10.3390/jcm11185482] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2022] [Revised: 09/08/2022] [Accepted: 09/14/2022] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND AND AIMS The presence of steatohepatitis in obese patients can be multifactorial. The current study tries to determine the differences between diabetic and non-diabetic patients regarding the presence of steatohepatitis. We evaluated sequential liver samples and collected the times of bariatric surgery to assess the presence of NASH in patients with obesity, in the circuit of bariatric surgery. METHODS We performed a retrospective study of 49 patients presenting high-grade obesity in the circuit of bariatric surgery, with liver biopsy. The patients underwent bariatric surgery at a single center in France and were followed for 2 years. The liver biopsies were performed intraoperatively on all 49 patients before the bariatric surgery. The primary endpoint of the study was to evaluate the relationships between steatohepatitis/liver fibrosis and the presence of diabetes and to evaluate the current relationships between the biochemical work-ups. Special importance was accorded to the correlations between vitamin D levels and the presence of hepatic steatosis, due to the antifibrogenic pattern in the liver, as shown in many important papers in the field. RESULTS Significant correlations were found between the presence of liver fibrosis and the presence of diabetes (p = 0.022), but not regarding the antidiabetic treatment. An important correlation was found between the vitamin D levels and the presence of liver fibrosis, as well as with the levels of A1C hemoglobin and LDL cholesterol levels. CONCLUSIONS Vitamin D deficiency presents a strong correlation with hepatic steatosis in individuals with morbid obesity. Correcting vitamin D deficiency may present a beneficial role in treating hepatic steatosis, diabetes, and cardiovascular risk in patients with morbid obesity.
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Liu Y, Shuai P, Liu Y, Li D. Association between non-alcoholic fatty liver disease and bone turnover markers in southwest China. J Bone Miner Metab 2022; 40:712-719. [PMID: 35639173 DOI: 10.1007/s00774-022-01340-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2021] [Accepted: 05/03/2022] [Indexed: 02/06/2023]
Abstract
INTRODUCTION Non-alcoholic fatty liver disease (NAFLD) is not considered only a liver disease but also associated with an increased risk of extra-hepatic diseases including bone metabolism disorders. In our study, we aim to explore the changes of several bone turnover markers (BTMs) under different fat deposition and stiffness levels of the liver. MATERIALS AND METHODS We analyzed the physical examination data of 3353 subjects from February 2018 to June 2021 in this study. The steatosis and stiffness of liver were quantitatively detected using the fat attenuation parameter (FAP) and liver stiffness measurements (LSM) of transient elastography (TE). Serum 25-hydroxyvitamin D3 (25(OH)D3), osteocalcin, carboxy-terminal collagen crosslinks (CTX), amino terminal elongation peptide of total type 1 procollagen (P1NP) were tested. Clinical and other biochemical data were also collected. RESULTS With the increasing of FAP, the levels of 25(OH)D3 and osteocalcin decreased, the difference was statistically significant. No correlation was found between LSM and all the four BTMs. Logistic regression analysis revealed that FAP ≥ 244 dB/m was negatively correlated with 25(OH)D3 (in both males and females) and osteocalcin (only in males). No correlation was found between FAP ≥ 244 dB/m and P1NP or CTX. CONCLUSION The degree of liver adipose deposition was found to be negatively associated with the serum levels of 25(OH)D3 (in both males and females) and osteocalcin (only in males) in southwest China.
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Affiliation(s)
- Ying Liu
- Department of Health Management Center and Institute of Health Management, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, 611731, Sichuan Province, China
- Department of Health Management Center and Institute of Health Management, Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, No. 32 Section 2, West 1st Ring Road, Qingyang District, Chengdu, 610072, Sichuan Province, China
| | - Ping Shuai
- Department of Health Management Center and Institute of Health Management, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, 611731, Sichuan Province, China
- Department of Health Management Center and Institute of Health Management, Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, No. 32 Section 2, West 1st Ring Road, Qingyang District, Chengdu, 610072, Sichuan Province, China
| | - Yuping Liu
- Department of Health Management Center and Institute of Health Management, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, 611731, Sichuan Province, China
- Department of Health Management Center and Institute of Health Management, Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, No. 32 Section 2, West 1st Ring Road, Qingyang District, Chengdu, 610072, Sichuan Province, China
| | - Dongyu Li
- Department of Health Management Center and Institute of Health Management, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, 611731, Sichuan Province, China.
- Department of Health Management Center and Institute of Health Management, Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, No. 32 Section 2, West 1st Ring Road, Qingyang District, Chengdu, 610072, Sichuan Province, China.
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Trimarco V, Manzi MV, Mancusi C, Strisciuglio T, Fucile I, Fiordelisi A, Pilato E, Izzo R, Barbato E, Lembo M, Morisco C. Insulin Resistance and Vitamin D Deficiency: A Link Beyond the Appearances. Front Cardiovasc Med 2022; 9:859793. [PMID: 35369303 PMCID: PMC8968037 DOI: 10.3389/fcvm.2022.859793] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2022] [Accepted: 02/17/2022] [Indexed: 12/23/2022] Open
Abstract
Vitamin D is a steroid hormone that plays a key role in the regulation of body homeostasis, including cardiovascular function. Although the chronic deficiency of vitamin D is associated with cardiovascular risk factors, as well as with an adverse prognosis, randomized controlled trials have failed in demonstrating that dietary vitamin D supplementation could ameliorate the prognosis of patients with cardiovascular diseases, and suggested that vitamin D deficiency is the expression of the effects of other determinants of cardiovascular risk. Thus, the supplementation of vitamin D is not sufficient to improve the cardiovascular risk profile and prognosis. Insulin resistance is a complex phenomenon that plays a key role in the pathogenesis of conventional cardiovascular risk factors. Interestingly, defects of vitamin D and insulin resistance have a superimposable epidemiological distribution. According to the common view, Insulin resistance is considered the direct or indirect consequence of vitamin D deficiency. However, it is also reasonable to speculate that the deficit or the impaired action of vitamin D, in some circumstances, could be the result of the same pathogenic mechanisms responsible of insulin resistance development. In this case, vitamin D deficiency could be considered an epiphenomenon of insulin resistance. Insulin resistance is a reversible condition, being possibly ameliorated by physical activity and hypocaloric diets. Notably, both physical exercise and energy-restricted dietary regimens are associated with an increase of vitamin D levels. These findings indicate that improving insulin resistance condition is a necessary step to ameliorate vitamin D supplementation-based strategies in cardiovascular prevention.
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Affiliation(s)
- Valentina Trimarco
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
| | - Maria Virginia Manzi
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
| | - Costantino Mancusi
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
| | - Teresa Strisciuglio
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
| | - Ilaria Fucile
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
| | - Antonella Fiordelisi
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
| | - Emanuele Pilato
- Department of Cardiac Surgery, School of Medicine, University of Naples Federico II, Naples, Italy
| | - Raffaele Izzo
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
| | - Emanuele Barbato
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
| | - Maria Lembo
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
- *Correspondence: Maria Lembo
| | - Carmine Morisco
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
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14
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Bennouar S, Cherif AB, Kessira A, Bennouar DE, Abdi S. Association and interaction between vitamin D level and metabolic syndrome for non-alcoholic fatty liver disease. J Diabetes Metab Disord 2021; 20:1309-1317. [PMID: 34900782 PMCID: PMC8630213 DOI: 10.1007/s40200-021-00857-5] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2021] [Accepted: 07/10/2021] [Indexed: 12/12/2022]
Abstract
INTRODUCTION/OBJECTIVES Previous studies have shown conflicting results regarding the association between hypovitaminosis D and non-alcoholic fatty liver disease (NAFLD). The aim of this study is to explore the individual and combined effect of hypovitaminosis D and metabolic syndrome (MS) on NAFLD. MATERIALS AND METHODS In this cross-sectional study, 874 subjects were enrolled. 25(OH)D was assessed by a sequential competitive immuno-fluoro-assay method. The Fatty Liver Index (FLI) was used for NAFLD screening. Binary logistic regression and additive interaction were performed to investigate the association between vitamin D status, MS and NAFLD. RESULTS Severe vitamin D deficiency was found to be positively related to NAFLD, with a higher risk in women than in men (OR = 6.4, 95% CI [2.8-15], p < 0.0001 vs. OR = 5.8, 95% CI [1.9-17.7], p = 0.002). In men, this association was partially masked by obesity. The additive interaction with MS was significant in women but not in men, the relative excess risk due to interaction was of 7.2, 95% CI [1.3-12.9], p = 0.02), the attributable proportion due to the combined effect was of 0.6, 95% CI [0.4-0.8], p < 0.0001. The interaction mechanism is synergistic; the synergy index: was of 2.9, 95% CI [1.6-5.3], p = 0.0006. CONCLUSION A positive association has been found between severe vitamin D deficiency and NAFLD. Moreover, an excess risk in women combining both MS and severe vitamin D deficiency was quantified.
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Affiliation(s)
- Salam Bennouar
- Central Laboratory of Clinical Biology, Frantz Fanon Hospital, University Hospital center of Blida, 9000 Blida, Algeria
| | - Abdelghani Bachir Cherif
- Department of Internal Medicine and Cardiology, University Hospital Center of Blida, 9000 Blida, Algeria
| | - Amel Kessira
- Department of hemobiology and Blood Transfusion, University Hospital Center of Annaba, 23000 Annaba, Algeria
| | - Djamel Eddine Bennouar
- Department of hemobiology and Blood Transfusion, University Hospital Center of Annaba, 23000 Annaba, Algeria
| | - Samia Abdi
- Central Laboratory of Clinical Biology, Frantz Fanon Hospital, University Hospital center of Blida, 9000 Blida, Algeria
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Pal P, Palui R, Ray S. Heterogeneity of non-alcoholic fatty liver disease: Implications for clinical practice and research activity. World J Hepatol 2021; 13:1584-1610. [PMID: 34904031 PMCID: PMC8637673 DOI: 10.4254/wjh.v13.i11.1584] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2021] [Revised: 07/29/2021] [Accepted: 10/14/2021] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a heterogeneous condition with a wide spectrum of clinical presentations and natural history and disease severity. There is also substantial inter-individual variation and variable response to a different therapy. This heterogeneity of NAFLD is in turn influenced by various factors primarily demographic/dietary factors, metabolic status, gut microbiome, genetic predisposition together with epigenetic factors. The differential impact of these factors over a variable period of time influences the clinical phenotype and natural history. Failure to address heterogeneity partly explains the sub-optimal response to current and emerging therapies for fatty liver disease. Consequently, leading experts across the globe have recently suggested a change in nomenclature of NAFLD to metabolic-associated fatty liver disease (MAFLD) which can better reflect current knowledge of heterogeneity and does not exclude concomitant factors for fatty liver disease (e.g. alcohol, viral hepatitis, etc.). Precise identification of disease phenotypes is likely to facilitate clinical trial recruitment and expedite translational research for the development of novel and effective therapies for NAFLD/MAFLD.
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Affiliation(s)
- Partha Pal
- Department of Medical Gastroenterology, Asian Institute of Gastroenterology, Hyderabad 500082, India
| | - Rajan Palui
- Department of Endocrinology, The Mission Hospital, Durgapur 713212, West Bengal, India
| | - Sayantan Ray
- Department of Endocrinology, Jagannath Gupta Institute of Medical Sciences and Hospital, Kolkata 700137, West Bengal, India
- Diabetes and Endocrinology, Apollo Clinic, Ballygunge, Kolkata 700019, West Bengal, India.
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Heo NJ, Park HE, Yoon JW, Kwak MS, Yang JI, Chung SJ, Yim JY, Chung GE. The Association between Vitamin D and Nonalcoholic Fatty Liver Disease Assessed by Controlled Attenuation Parameter. J Clin Med 2021; 10:jcm10122611. [PMID: 34199258 PMCID: PMC8231966 DOI: 10.3390/jcm10122611] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2021] [Revised: 06/10/2021] [Accepted: 06/11/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND An association between nonalcoholic fatty liver disease (NAFLD) and low vitamin D levels has been suggested. We investigated the relationship between vitamin D and NAFLD assessed by controlled attenuation parameter (CAP). METHODS We conducted a retrospective cohort study of apparently healthy subjects who underwent Fibroscan during health screening tests. NAFLD was diagnosed using CAP values. RESULTS Among the 1202 subjects (mean age 57.2 years, 60.6% male), 630 (52.4%) subjects had NAFLD with CAP ≥ 248 dB/m. Multivariable analysis was conducted after adjusting for metabolic risk factors including diabetes, hypertension, hypercholesterolemia, body mass index, high-density lipoprotein cholesterol, triglyceride and smoking. Higher vitamin D levels showed a lower risk of NAFLD compared to the lowest quartile of vitamin D in a dose-dependent manner (OR 0.68, 95% CI 0.47-1.00 in Q2 vs. Q1; OR 0.65, 95% CI 0.44-0.94 in Q3 vs. Q1; and OR 0.64, 95% CI 0.44-0.94 in Q4 vs. Q1). The highest quartile of vitamin D showed a decreased risk of a severe grade of steatosis (CAP ≥ 302 dB/m) compared to the lowest quartile (OR 0.52, 95% CI 0.31-0.87 in Q4 vs. Q1). CONCLUSIONS Higher levels of serum vitamin D were associated with a decreased risk of CAP-defined NAFLD, compared to low levels of serum vitamin D. The association between NAFLD and vitamin D suggests that vitamin D may exert a protective role against NAFLD.
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Affiliation(s)
- Nam Ju Heo
- Department of Nephrology, Internal Medicine, Seoul National University Hospital Healthcare System Gangnam Center, Seoul 06236, Korea;
| | - Hyo Eun Park
- Department of Cardiology, Internal Medicine, Seoul National University Hospital Healthcare System Gangnam Center, Seoul 06236, Korea;
| | - Ji Won Yoon
- Department of Endocrinology, Internal Medicine, Seoul National University Hospital Healthcare System Gangnam Center, Seoul 06236, Korea;
| | - Min-Sun Kwak
- Department of Gastroenterology and Hepatology, Internal Medicine, Seoul National University Hospital Healthcare System Gangnam Center, Seoul 03080, Korea; (M.-S.K.); (J.I.Y.); (S.J.C.); (J.Y.Y.)
| | - Jong In Yang
- Department of Gastroenterology and Hepatology, Internal Medicine, Seoul National University Hospital Healthcare System Gangnam Center, Seoul 03080, Korea; (M.-S.K.); (J.I.Y.); (S.J.C.); (J.Y.Y.)
| | - Su Jin Chung
- Department of Gastroenterology and Hepatology, Internal Medicine, Seoul National University Hospital Healthcare System Gangnam Center, Seoul 03080, Korea; (M.-S.K.); (J.I.Y.); (S.J.C.); (J.Y.Y.)
| | - Jeong Yoon Yim
- Department of Gastroenterology and Hepatology, Internal Medicine, Seoul National University Hospital Healthcare System Gangnam Center, Seoul 03080, Korea; (M.-S.K.); (J.I.Y.); (S.J.C.); (J.Y.Y.)
| | - Goh Eun Chung
- Department of Gastroenterology and Hepatology, Internal Medicine, Seoul National University Hospital Healthcare System Gangnam Center, Seoul 03080, Korea; (M.-S.K.); (J.I.Y.); (S.J.C.); (J.Y.Y.)
- Correspondence: ; Tel.: +82-(0)2-2112-5741; Fax: +82-(0)2-2112-5635
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Wang Q, Shi X, Wang J, Zhang J, Xu C. Low serum vitamin D concentrations are associated with obese but not lean NAFLD: a cross-sectional study. Nutr J 2021; 20:30. [PMID: 33794916 PMCID: PMC8017627 DOI: 10.1186/s12937-021-00690-9] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2020] [Accepted: 03/25/2021] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND A low serum vitamin D concentration has been reported to be associated with an increased risk of non-alcoholic fatty liver disease (NAFLD); however, whether lean or obese individuals show a similar association between vitamin D and NAFLD remains speculative. This study aimed to explore the relationship between serum vitamin D concentration and NAFLD in lean and obese Chinese adults. METHODS This cross-sectional study included 2538 participants (1360 men and 1178 women) who underwent health checkups at the First Affiliated Hospital, Zhejiang University School of Medicine in 2019. NAFLD was diagnosed by liver ultrasound excluding other causes. The association of serum vitamin D concentration with NAFLD was analyzed in lean and obese participants. RESULTS The overall prevalence of NAFLD was 33.61% (13.10% in lean and 53.32% in obese) in this study population. The serum vitamin D levels of obese NAFLD patients were lower than those of obese NAFLD-free controls. However, the serum vitamin D levels of lean NAFLD patients were comparable to those of lean NAFLD-free controls. Serum vitamin D level was negatively correlated with the prevalence of NAFLD in obese but not lean participants. Serum vitamin D level was independently associated with the risk of NAFLD in obese participants, with an adjusted odds ratio (95% CI) of 0.987 (0.981-0.993). However, serum vitamin D level was not related to the risk of NAFLD in lean participants. CONCLUSIONS A low serum vitamin D level is associated with NAFLD in obese but not lean participants.
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Affiliation(s)
- Qinqiu Wang
- Department of Gastroenterology, the First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, China
| | - Xiaoying Shi
- Department of Gastroenterology, the First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, China
| | - Jinghua Wang
- Department of Gastroenterology, the First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, China
| | - Juanwen Zhang
- Department of Laboratory Medicine, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China
| | - Chengfu Xu
- Department of Gastroenterology, the First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, China.
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Cheng YM, Kao JH, Wang CC. The metabolic profiles and body composition of lean metabolic associated fatty liver disease. Hepatol Int 2021; 15:405-412. [PMID: 33539004 DOI: 10.1007/s12072-021-10147-0] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2020] [Accepted: 01/18/2021] [Indexed: 12/17/2022]
Abstract
BACKGROUND/PURPOSE Metabolic associated fatty liver disease (MAFLD) is the commonest cause of chronic liver disease, which is associated with obesity and diabetes. However, it also occurs in lean individuals especially in Asian populations. METHODS The participants of Tzu Chi MAFLD cohort (TCMC) including health controls or MAFLD patients were enrolled. MAFLD was defined as fatty liver in imaging without hepatitis B virus, hepatitis C virus infection, drug, alcohol or other known causes of chronic liver disease. Lean MAFLD was defined as MAFLD in lean subjects (BMI < 23 kg/m2). RESULTS A total of 880 subjects were included for final analysis. Of 394 MAFLD patients, 65 (16.5%) patients were diagnosed as lean MAFLD. Lean MAFLD patients were elder, higher percentage of female gender, lower ALT, diastolic blood pressure, triglyceride, and waist circumference but higher HDL than non-lean MAFLD patients. Using binary regression analysis, elder age and lower waist circumference were associated with lean MAFLD. Compared with lean healthy controls, lean MAFLD patients had higher BMI, waist circumference, and percentage of hypertension. In body composition, fatty tissue index (FTI), lean tissue index (LTI) ,and total body water (TBW) were lower in lean MAFLD than non-lean MAFLD patients; but they were comparable with lean healthy controls. CONCLUSIONS The prevalence of lean MAFLD was 16.5% in this study population and it was higher in elder age, especially of female subjects. Lean MAFLD patients had different metabolic profiles compared with lean healthy controls, but different body composition compared with non-lean MAFLD patients.
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Affiliation(s)
- Yu-Ming Cheng
- Department of Gastroenterology, Buddhist Tzu Chi Medical Foundation and School of Medicine, Taipei Tzu Chi Hospital, Tzu Chi University, 289 Jianguo Rd., Xindian area, New Taipei City, Hualien, 23142, Taiwan
| | - Jia-Horng Kao
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Chia-Chi Wang
- Department of Gastroenterology, Buddhist Tzu Chi Medical Foundation and School of Medicine, Taipei Tzu Chi Hospital, Tzu Chi University, 289 Jianguo Rd., Xindian area, New Taipei City, Hualien, 23142, Taiwan.
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Li H, Ma J, Gu L, Chen P, Chen L, Zhang X. Serum Glycocholic Acid‐to‐Total Bile Acid Ratio Is Independently Associated with Nonalcoholic Fatty Liver Disease: A Retrospective Cross‐Sectional Study. BIOMED RESEARCH INTERNATIONAL 2021; 2021. [DOI: 10.1155/2021/6698085] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/25/2020] [Accepted: 02/16/2021] [Indexed: 09/01/2023]
Abstract
Introduction and Aims. Bile acids play an essential role in the progression of nonalcoholic fatty liver disease (NAFLD). This study was aimed at investigating the association of the serum glycocholic acid‐ (GCA‐) to‐total bile acid (TBA) ratio with NAFLD in the general population. Materials and Methods. A total of 6708 subjects (2859 cases with NAFLD and 3849 controls) were enrolled in the development cohort and additional 1568 subjects (784 cases with NAFLD and 784 controls) in an independent validation cohort. Demographic characteristics and biochemical data were compared between subjects with NAFLD and controls. Multivariate logistic regression analysis was performed to determine the association of the GCA‐to‐TBA ratio with NAFLD. A novel model incorporating the GCA‐to‐TBA ratio was developed for screening NAFLD from the general population. Results. The serum TBA and GCA levels were significantly higher in subjects with NAFLD than in those without NAFLD (2.8 (2.0‐4.2) μmol/L vs. 2.5 (1.8‐3.7) μmol/L and 1.30 (1.10‐1.53) μg/mL vs. 1.28 (1.08‐1.50) μg/mL, respectively, all p ≤ 0.01), whereas the serum GCA‐to‐TBA ratio was significantly lower in subjects with NAFLD than in subjects without NAFLD (0.44 (0.33‐0.60) vs. 0.48 (0.36‐0.64), p ≤ 0.01). Logistic regression analysis showed that the GCA‐to‐TBA ratio was independently associated with NAFLD after adjustment for confounding factors (odds ratio: 0.81, 95% confidence interval (CI): 0.71‐0.92, p ≤ 0.01). The area under the receiver operating characteristic curve of the novel developed GCA‐to‐TBA ratio score model in discriminating NAFLD was 0.84 (95% CI: 0.83‐0.85) in the development cohort and was 0.91 (95% CI: 0.36‐0.65) in the validation cohort. Conclusion. The serum GCA‐to‐TBA ratio is independently associated with NAFLD. A simple novel model incorporating the GCA‐to‐TBA ratio score has a good performance in discriminating NAFLD from the general population.
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20
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Association between blood cadmium and vitamin D levels in the Yangtze Plain of China in the context of rapid urbanization. Chin Med J (Engl) 2020; 134:53-59. [PMID: 32925289 PMCID: PMC7862803 DOI: 10.1097/cm9.0000000000001068] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023] Open
Abstract
BACKGROUND China has experienced rapid urbanization in the past 30 years. We aimed to report blood cadmium level (BCL) in the rapidly urbanized Yangtze Plain of China, and explore the association between BCL and 25-hydroxyvitamin D (25(OH)D). METHODS Our data source was the Survey on Prevalence in East China for Metabolic Diseases and Risk Factors (SPECT-China) cross-sectional study (ChiCTR-ECS-14005052, www.chictr.org). We enrolled 3234 subjects from 12 villages in the Yangtze Plain. BCLs were measured by atomic absorption spectrometry. 25(OH)D was measured with a chemiluminescence assay. RESULTS A total of 2560 (79.2%) subjects were diagnosed with vitamin D deficiency. The median (interquartile range) BCL was 1.80 μg/L (0.60-3.42) for men and 1.40 μg/L (0.52-3.10) for women. In women, mean 25(OH)D concentrations were inversely associated with BCL (0.401, 95% confidence interval: -0.697 to -0.105 nmol/L lower with each doubling of the BCL) after adjustment for age, educational status, current smoking, body mass index, diabetes, and season. However, there was no significant difference in 25(OH)D across the BCL tertiles for men. CONCLUSIONS BCL in Chinese residents in the Yangtze Plain were much higher than that in developed countries. An inverse association between BCL and 25(OH)D was found in general Chinese women after multivariable adjustment. Future prospective cohort and animal studies are warranted to resolve the direction and temporality of these relationships, and to elucidate the exact mechanisms involved.
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21
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Zelber-Sagi S, Zur R, Thurm T, Goldstein A, Ben-Assuli O, Chodick G, Shibolet O. Low serum vitamin D is independently associated with unexplained elevated ALT only among non-obese men in the general population. Ann Hepatol 2020; 18:578-584. [PMID: 31103458 DOI: 10.1016/j.aohep.2019.03.006] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2018] [Revised: 02/05/2019] [Accepted: 03/05/2019] [Indexed: 02/08/2023]
Abstract
INTRODUCTION AND OBJECTIVES There are inconsistent findings on the association between human non-alcoholic fatty liver disease (NAFLD) and vitamin D, perhaps due to insufficient specificity for gender and obesity status. We aimed to assess whether serum levels of 25-hydroxyvitamin D are associated with unexplained elevated alanine aminotransferase (ALT) in general population across gender and body mass index (BMI) levels. MATERIALS AND METHODS A cross-sectional analysis of a population-based cohort with a nationwide-distribution using electronic medical database. The population consisted of individuals aged 20-60 years who underwent blood tests for ALT and vitamin D. RESULTS A total of 82,553 subjects were included (32.5% men, mean age 43.91±10.15 years). The prevalence of elevated ALT was higher among men and women with vitamin D insufficiency or deficiency, but in multivariate analysis, adjusting for: age, BMI, serum levels of glucose, total cholesterol, triglycerides, statin use and season, only the association among men remained significant for the vitamin D deficiency category (OR=1.16, 95%CI 1.04-1.29, P=0.010). Stratification by BMI revealed that only among normal weight and overweight men vitamin D deficiency was associated with elevated ALT (OR=1.27, 95%CI 1.01-1.59, P=0.041 and OR=1.27, 95%CI 1.08-1.50, P=0.003, respectively). No independent association was shown among women at all BMI categories. CONCLUSIONS In a "real-life" general population, the association between vitamin D deficiency and unexplained elevated ALT is specific for non-obese men. The clinical significance of vitamin D for human NAFLD should be further elucidated with attention for a modifying effect of gender and adiposity.
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Affiliation(s)
- Shira Zelber-Sagi
- Faculty of Social Welfare and Health Sciences, School of Public Health, University of Haifa, Israel; The Liver Unit, Gastroenterology Department, Tel-Aviv Medical Center, Israel.
| | - Reut Zur
- Faculty of Social Welfare and Health Sciences, School of Public Health, University of Haifa, Israel
| | - Tamar Thurm
- The Liver Unit, Gastroenterology Department, Tel-Aviv Medical Center, Israel
| | - Alex Goldstein
- Medical Division, Maccabi Healthcare Services, Tel Aviv, Israel
| | - Ofir Ben-Assuli
- Faculty of Business Administration, Ono Academic College, Israel
| | - Gabriel Chodick
- Medical Division, Maccabi Healthcare Services, Tel Aviv, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Oren Shibolet
- The Liver Unit, Gastroenterology Department, Tel-Aviv Medical Center, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
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22
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Dutra JDM, Lisboa QC, Ferolla SM, Carvalho CMML, Mendes CCM, Ferrari TCA, Couto CA. Vitamin D levels are not associated with non-alcoholic fatty liver disease severity in a Brazilian population. INT J VITAM NUTR RES 2020; 91:411-418. [PMID: 32639223 DOI: 10.1024/0300-9831/a000667] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
Some epidemiological evidence suggests an inverse correlation between non-alcoholic fatty liver disease (NAFLD) frequency and vitamin D levels. Likewise, a beneficial effect of vitamin D on diabetes mellitus (DM) and insulin resistance has been observed, but this is an unsolved issue. Thus, we aimed to investigate the prevalence of hypovitaminosis D in a NAFLD Brazilian population and its association with disease severity and presence of comorbidities. In a cross-sectional study, the clinical, biochemical and histological parameters of 139 NAFLD patients were evaluated according to two different cut-off points of serum 25-hydroxyvitamin D levels (20 ng/mL and 30 ng/mL). The mean age of the population was 56 ± 16 years, most patients were female (83%), 72% had hypertension, 88% dyslipidemia, 46% DM, 98% central obesity, and 82% metabolic syndrome. Serum vitamin D levels were < 30 ng/mL in 78% of the patients, and < 20 ng/mL in 35%. The mean vitamin D level was 24.3 ± 6.8 ng/mL. The comparison between the clinical, biochemical and histological characteristics of the patients according to the levels of vitamin D showed no significant difference. Most patients with NAFLD had hypovitaminosis D, but low vitamin D levels were not related to disease severity and the presence of comorbidities.
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Affiliation(s)
- Jeniffer Danielle M Dutra
- Departamento de Clínica Médica, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
| | - Quelson Coelho Lisboa
- Departamento de Clínica Médica, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
| | - Silvia Marinho Ferolla
- Departamento de Clínica Médica, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
| | - Carolina Martinelli M L Carvalho
- Instituto Alfa de Gastroenterologia do Hospital das Clínicas, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
| | - Camila Costa M Mendes
- Instituto Alfa de Gastroenterologia do Hospital das Clínicas, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
| | - Teresa Cristina A Ferrari
- Departamento de Clínica Médica, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.,Instituto Alfa de Gastroenterologia do Hospital das Clínicas, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
| | - Cláudia Alves Couto
- Departamento de Clínica Médica, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.,Instituto Alfa de Gastroenterologia do Hospital das Clínicas, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
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23
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Mitra S, De A, Chowdhury A. Epidemiology of non-alcoholic and alcoholic fatty liver diseases. Transl Gastroenterol Hepatol 2020; 5:16. [PMID: 32258520 PMCID: PMC7063528 DOI: 10.21037/tgh.2019.09.08] [Citation(s) in RCA: 329] [Impact Index Per Article: 65.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2019] [Accepted: 09/05/2019] [Indexed: 12/12/2022] Open
Abstract
Liver diseases are fast emerging as global health priorities. Fatty liver is described in the setting of non-alcoholic fatty liver disease (NAFLD) as well as alcoholic liver disease (ALD), the pathogenesis of excess fat being different in the two conditions while both are important components of the changing face of burden of liver diseases worldwide. They are intimately associated with a globalized economy and an increasingly homogenous socio- cultural order with a westernized lifestyle. The accompanying adoption of a progressively sedentary life, consumption of diet dense in calories facilitate development of NAFLD while a spiraling upward trend in alcohol use along with earlier age of drinking as well as increased amount of per capita alcohol consumption increases the prevalence of ALD globally. Adverse health outcomes in NAFLD as well as ALD are caused not only by progressive liver fibrosis that is the most significant factor for liver related and all-cause mortality in both but also by non-liver (cardiovascular, cancer, accidents, neurological) clinical outcomes that calls for a multidisciplinary and social approach to these conditions. We present here an outline of facets of epidemiology of both NAFLD as well as ALD along with its' public health implications. A broad-based integrated approach that incorporates social, behavioral as well as biological targets need to be undertaken at a health system level in a planned manner for these evolving liver health priorities that disproportionately challenges the low- and middle-income countries of Asia, South America and Africa.
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Affiliation(s)
- Souveek Mitra
- Indian Institute of Liver and Digestive Sciences Sitala (east), Jagadishpur, Sonarpur, Kolkata, India
| | - Arka De
- Department of Hepatology, Post Graduate Institute of Medical Education and Research Chandigarh, Chandigarh, India
| | - Abhijit Chowdhury
- Indian Institute of Liver and Digestive Sciences Sitala (east), Jagadishpur, Sonarpur, Kolkata, India
- Department of Hepatology School of Digestive and Liver Diseases Institute of Post Graduate Medical Education & Research Kolkata, India
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24
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Wang X, Chen X, Zhang H, Pang J, Lin J, Xu X, Yang L, Ma J, Ling W, Chen Y. Circulating retinol-binding protein 4 is associated with the development and regression of non-alcoholic fatty liver disease. DIABETES & METABOLISM 2020; 46:119-128. [DOI: 10.1016/j.diabet.2019.04.009] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/12/2019] [Revised: 04/28/2019] [Accepted: 04/28/2019] [Indexed: 02/07/2023]
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25
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Zeng Y, Luo M, Pan L, Chen Y, Guo S, Luo D, Zhu L, Liu Y, Pan L, Xu S, Zhang R, Zhang C, Wu P, Ge L, Noureddin M, Pandol SJ, Han YP. Vitamin D signaling maintains intestinal innate immunity and gut microbiota: potential intervention for metabolic syndrome and NAFLD. Am J Physiol Gastrointest Liver Physiol 2020; 318:G542-G553. [PMID: 31984787 PMCID: PMC7099486 DOI: 10.1152/ajpgi.00286.2019] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2019] [Revised: 12/13/2019] [Accepted: 01/19/2020] [Indexed: 01/31/2023]
Abstract
A lack of sunlight exposure, residence in the northern latitudes, and dietary vitamin D insufficiency are coprevalent with metabolic syndrome (MetS), Type 2 diabetes (T2D), and nonalcoholic fatty liver diseases (NAFLD), implying a potential causality and underlying mechanism. Whether vitamin D supplementation or treatment can improve these disorders is controversial, in part, because of the absence of large-scale trials. Experimental investigations, on the other hand, have uncovered novel biological functions of vitamin D in development, tumor suppression, and immune regulation, far beyond its original role as a vitamin that maintained calcium homeostasis. While the large intestine harbors massive numbers of microbes, the small intestine has a minimal quantity of bacteria, indicating the existence of a gating system located in the distal region of the small intestine that may restrain bacterial translocation to the small intestine. Vitamin D receptor (VDR) was found to be highly expressed at the distal region of small intestine, where the vitamin D signaling promotes innate immunity, including the expression of α-defensins by Paneth cells, and maintains the intestinal tight junctions. Thus, a new hypothesis is emerging, indicating that vitamin D deficiency may impair the intestinal innate immunity, including downregulation of Paneth cell defensins, leading to bacterial translocation, endotoxemia, systemic inflammation, insulin resistance, and hepatic steatosis. Here, we review the studies for vitamin D for innate immunity and metabolic homeostasis, and we outline the clinical trials of vitamin D for mitigating MetS, T2D, and NAFLD.
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Affiliation(s)
- Yilan Zeng
- Chengdu Public Health Clinical Center, Chengdu, China
| | - Mei Luo
- Chengdu Public Health Clinical Center, Chengdu, China
| | - Liwei Pan
- The Center for Growth, Metabolism and Aging, College of Life Sciences, Sichuan University, Chengdu, China
| | - Yuan Chen
- The Center for Growth, Metabolism and Aging, College of Life Sciences, Sichuan University, Chengdu, China
| | - Siqi Guo
- The Center for Growth, Metabolism and Aging, College of Life Sciences, Sichuan University, Chengdu, China
| | - Dongxia Luo
- Chengdu Public Health Clinical Center, Chengdu, China
| | - Li Zhu
- Chengdu Public Health Clinical Center, Chengdu, China
| | - Yong Liu
- Chengdu Public Health Clinical Center, Chengdu, China
| | - Lisha Pan
- The Center for Growth, Metabolism and Aging, College of Life Sciences, Sichuan University, Chengdu, China
| | - Siya Xu
- The Center for Growth, Metabolism and Aging, College of Life Sciences, Sichuan University, Chengdu, China
| | - Ruofei Zhang
- The Center for Growth, Metabolism and Aging, College of Life Sciences, Sichuan University, Chengdu, China
| | - Chunyan Zhang
- The Center for Growth, Metabolism and Aging, College of Life Sciences, Sichuan University, Chengdu, China
| | - Pengfei Wu
- The Center for Growth, Metabolism and Aging, College of Life Sciences, Sichuan University, Chengdu, China
| | - Liangpeng Ge
- Chongqing Academy of Animal Sciences, Chongqing, China
| | | | | | - Yuan-Ping Han
- The Center for Growth, Metabolism and Aging, College of Life Sciences, Sichuan University, Chengdu, China
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26
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Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease which may progress to non-alcoholic steatohepatitis. The prevalence of sarcopenia, which is the loss of muscle mass and strength, is increasing in the aging society. Recent studies reported the relationship between NAFLD and sarcopenia. The skeletal muscle is the primary organ for glucose disposal. Loss of muscle mass can cause insulin resistance, which is an important risk factor for NAFLD. Moreover, obesity, chronic low-grade inflammation, vitamin D deficiency, physical inactivity, hepatokines, and myokines might be involved in the pathophysiologic mechanism of sarcopenia and NAFLD. Although most of the previous studies have demonstrated the positive correlation between sarcopenia and NAFLD, the difference in diagnostic methods of sarcopenia and NAFLD leads to difficulties in interpretation and application. This review discusses the concept and diagnosis of sarcopenia and NAFLD, common pathophysiology, and clinical studies linking sarcopenia to NAFLD. The presentation of the association between sarcopenia and NAFLD may provide an opportunity to prevent the deterioration of fatty liver disease.
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Affiliation(s)
- Jung A Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Korea University Guro Hospital, 148 Guro-Dong, Guro-Gu, Seoul, 08308, South Korea
| | - Kyung Mook Choi
- Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Korea University Guro Hospital, 148 Guro-Dong, Guro-Gu, Seoul, 08308, South Korea.
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27
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Caporaso NE, Jones RR, Stolzenberg-Solomon RZ, Medgyesi DN, Kahle LL, Graubard BI. Insulin Resistance in Healthy U.S. Adults: Findings from the National Health and Nutrition Examination Survey (NHANES). Cancer Epidemiol Biomarkers Prev 2019; 29:157-168. [PMID: 31641012 DOI: 10.1158/1055-9965.epi-19-0206] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2019] [Revised: 05/07/2019] [Accepted: 10/01/2019] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND Insulin is fundamental in two conditions that are epidemic in the United States and globally: obesity and type II diabetes. Given insulin's established mechanistic involvement in energy balance and glucose tolerance, we examined its relationship to common health-related endpoints in a large population-based sample. METHODS The National Health and Nutrition Examination Survey is a cross-sectional study that uses a complex multistage probability design to obtain a representative sample of the United States population. Adult participants were included from 8 successive 2-year data waves (1999-2014), including 9,224 normal individuals, 7,699 prediabetic, and 3,413 diabetic subjects. The homeostatic model for insulin resistance (HOMA-IR) was available for 20,336 participants and its relationship with demographic, anthropometric, and clinical data was analyzed. We examined the relationship of HOMA-IR to 8 groups of outcome variables: general health, anthropometric/metabolic [waist size, body mass index (BMI)], cardiovascular (blood pressure), lipid [triglycerides, high-density lipoprotein (HDL)], hepatic [alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT)], hematologic [white blood cells (WBC), hemoglobin (Hgb), platelets], inflammatory (C-reactive protein), and nutritional (vitamins D and C, serum folate, and pyridoxine) variables. RESULTS HOMA-IR was generally strongly, monotonically, and highly significantly associated with adjusted outcomes in normal subjects, although clinical laboratory values were generally within normal bounds across insulin quartiles. In the normal subset, the odds ratio and 95% confidence interval for a quartile change in HOMA-IR for obesity (BMI > 30) was 3.62 (3.30-3.97), and for the highest quintile for the triglyceride/HDL the ratio was 2.00 (1.77-2.26), for GGT it was 1.40 (1.24-1.58), and for WBC it was 1.28 (1.16-1.40). The relationship of HOMA-IR to the various outcomes was broadly similar to that observed in prediabetics and diabetics with a few exceptions. CONCLUSIONS HOMA-IR levels in a large sample of normal individuals are associated with poorer general health and adverse changes across a wide range of markers. A similar pattern of alterations is observed in prediabetic and diabetic samples. IMPACT Clinically, checking insulin levels may be helpful to identify patients that merit further observation and are candidates for early interventions.
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Affiliation(s)
- Neil E Caporaso
- Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics (DCEG), National Cancer Institute (NCI), National Institutes of Health (NIH), Rockville, Maryland.
| | - Rena R Jones
- Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics (DCEG), National Cancer Institute (NCI), National Institutes of Health (NIH), Rockville, Maryland
| | | | - Danielle N Medgyesi
- Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics (DCEG), National Cancer Institute (NCI), National Institutes of Health (NIH), Rockville, Maryland
| | - Lisa L Kahle
- Information Management Services Inc., Calverton, Maryland
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28
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Kusu H, Yoshida H, Kudo M, Okuyama M, Harada N, Tsuji‐Naito K, Akagawa M. Tomatidine Reduces Palmitate‐Induced Lipid Accumulation by Activating AMPK via Vitamin D Receptor‐Mediated Signaling in Human HepG2 Hepatocytes. Mol Nutr Food Res 2019; 63:e1801377. [DOI: 10.1002/mnfr.201801377] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Affiliation(s)
- Hikari Kusu
- Division of Applied Life SciencesGraduate School of Life and Environmental SciencesOsaka Prefecture University Sakai 599‐8531 Japan
| | - Hiroki Yoshida
- Division of Applied Life SciencesGraduate School of Life and Environmental SciencesOsaka Prefecture University Sakai 599‐8531 Japan
| | - Michiko Kudo
- DHC Corporation LaboratoriesDivision 2, 2‐42 Hamada Mihama‐ku Chiba 261‐0025 Japan
| | - Mai Okuyama
- Division of Applied Life SciencesGraduate School of Life and Environmental SciencesOsaka Prefecture University Sakai 599‐8531 Japan
| | - Naoki Harada
- Division of Applied Life SciencesGraduate School of Life and Environmental SciencesOsaka Prefecture University Sakai 599‐8531 Japan
| | - Kentaro Tsuji‐Naito
- DHC Corporation LaboratoriesDivision 2, 2‐42 Hamada Mihama‐ku Chiba 261‐0025 Japan
| | - Mitsugu Akagawa
- Division of Applied Life SciencesGraduate School of Life and Environmental SciencesOsaka Prefecture University Sakai 599‐8531 Japan
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29
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Cimini FA, Barchetta I, Carotti S, Morini S, Cavallo MG. Overview of studies of the vitamin D/vitamin D receptor system in the development of non-alcoholic fatty liver disease. World J Gastrointest Pathophysiol 2019; 10:11-16. [PMID: 31559105 PMCID: PMC6751507 DOI: 10.4291/wjgp.v10.i2.11] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2019] [Revised: 08/09/2019] [Accepted: 08/21/2019] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the world. NAFLD is known to be associated with obesity, type 2 diabetes, metabolic syndrome and increased cardiovascular events: for these reasons, it is becoming a global public health problem and represents an important challenge in terms of prevention and treatment. The mechanisms behind the pathogenesis of NAFLD are multiple and have not yet been completely unraveled; consequently, at moment there are not effective treatments. In the past few years a large body of evidence has been assembled that attributes an important role in hepatic aberrant fat accumulation, inflammation and fibrosis, to the vitamin D/vitamin D receptor (VD/VDR) axis, showing a strong association between hypovitaminosis D and the diagnosis of NAFLD. However, the data currently available, including clinical trials with VD supplementation, still provides a contrasting picture. The purpose of this editorial is to provide an overview of recent advances in the pathogenesis of NAFLD in relation to VD/VDR. Based on recent data from literature, we focused in particular on the hypothesis that VDR itself, independently from its traditional ligand VD, may have a crucial function in promoting hepatic fat accumulation. This might also offer new possibilities for future innovative therapeutic approaches in the management of NAFLD.
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Affiliation(s)
- Flavia Agata Cimini
- Department of Experimental Medicine, Sapienza University of Rome, Rome I-00161, Italy
| | - Ilaria Barchetta
- Department of Experimental Medicine, Sapienza University of Rome, Rome I-00161, Italy
| | - Simone Carotti
- Department of Medicine and Surgery, Laboratory of Microscopic and Ultrastructural Anatomy, University Campus Bio-Medico of Rome, Rome I-00128, Italy
| | - Sergio Morini
- Department of Medicine and Surgery, Laboratory of Microscopic and Ultrastructural Anatomy, University Campus Bio-Medico of Rome, Rome I-00128, Italy
| | - Maria Gisella Cavallo
- Department of Experimental Medicine, Sapienza University of Rome, Rome I-00161, Italy
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30
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Hsing JC, Nguyen MH, Yang B, Min Y, Han SS, Pung E, Winter SJ, Zhao X, Gan D, Hsing AW, Zhu S, Wang CJ. Associations Between Body Fat, Muscle Mass, and Nonalcoholic Fatty Liver Disease: A Population-Based Study. Hepatol Commun 2019; 3:1061-1072. [PMID: 31388627 PMCID: PMC6671685 DOI: 10.1002/hep4.1392] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2019] [Accepted: 05/28/2019] [Indexed: 12/16/2022] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is one of the most common forms of liver disease worldwide and has emerged as a significant public health concern in China. A better understanding of the etiology of NAFLD can inform effective management strategies for this disease. We examined factors associated with NAFLD in two districts of Hangzhou, China, focusing on the relationship of regional body fat distribution, muscle mass, and NAFLD. We used baseline data to carry out a cross‐sectional analysis among 3,589 participants from the Wellness Living Laboratory (WELL) China study, a longitudinal population‐based study that aims to investigate and promote well‐being among the Chinese population. NAFLD was defined using the widely validated fatty liver index (FLI). Multivariate logistic regressions were performed to assess independent associations between NAFLD and metabolic risk factors (e.g., insulin resistance) and dual x‐ray absorptiometry (DXA)‐derived measures (e.g., android fat ratio [AFR] and skeletal muscle index [SMI]). Of the 3,589 participants, 476 (13.3%) were classified as having FLI‐defined NAFLD (FLI ≥60). Among those, 58.0% were men. According to our analysis, AFR (odds ratio [OR], 10.0; 95% confidence interval [CI], 5.8‐18.5), insulin resistance (OR, 4.0; 95% CI, 3.0‐5.3), high alanine aminotransferase levels (OR, 7.6; 95% CI, 5.8‐10.0), smoking (OR, 2.0; 95% CI, 1.4‐3.0), and male sex (OR, 2.9; 95% CI, 2.0‐4.2) were positively associated with NAFLD risk, while SMI (OR, 0.1; 95% CI, 0.07‐0.13) was inversely associated with NAFLD risk. Conclusion: In addition to known metabolic risk factors, DXA‐derived AFR and SMI may provide additional insights to the understanding of NAFLD. Interventions that aim to decrease AFR and increase SMI may be important to reduce the burden of NAFLD in this population.
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Affiliation(s)
- Julianna C Hsing
- Center for Policy, Outcomes and Prevention Stanford University School of Medicine Stanford CA.,Division of General Pediatrics Stanford University School of Medicine Stanford CA
| | - Mindie H Nguyen
- Division of Gastroenterology and Hepatology, Department of Medicine Stanford University School of Medicine Stanford CA.,Stanford Cancer Institute Stanford University School of Medicine Stanford CA
| | - Baiyu Yang
- Stanford Cancer Institute Stanford University School of Medicine Stanford CA
| | - Yan Min
- Stanford Prevention Research Center Stanford University School of Medicine Stanford CA
| | - Summer S Han
- Stanford Cancer Institute Stanford University School of Medicine Stanford CA.,Quantitative Sciences Unit, Department of Medicine Stanford University School of Medicine Stanford CA.,Department of Neurosurgery Stanford University School of Medicine Stanford CA
| | - Emily Pung
- Department of Public Health University of Maryland College Park MD
| | - Sandra J Winter
- Stanford Prevention Research Center Stanford University School of Medicine Stanford CA
| | - Xueyin Zhao
- Chronic Disease Research Institute, Department of Nutrition and Food Hygiene, School of Public Health Zhejiang University Hangzhou China.,Women's Hospital, School of Medicine Zhejiang University Hangzhou China
| | - Da Gan
- Chronic Disease Research Institute, Department of Nutrition and Food Hygiene, School of Public Health Zhejiang University Hangzhou China.,Women's Hospital, School of Medicine Zhejiang University Hangzhou China
| | - Ann W Hsing
- Stanford Cancer Institute Stanford University School of Medicine Stanford CA.,Stanford Prevention Research Center Stanford University School of Medicine Stanford CA
| | - Shankuan Zhu
- Chronic Disease Research Institute, Department of Nutrition and Food Hygiene, School of Public Health Zhejiang University Hangzhou China.,Women's Hospital, School of Medicine Zhejiang University Hangzhou China
| | - C Jason Wang
- Center for Policy, Outcomes and Prevention Stanford University School of Medicine Stanford CA.,Division of General Pediatrics Stanford University School of Medicine Stanford CA
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31
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López-Bautista F, Posadas-Romero C, Ruiz-Vargas LY, Cardoso-Saldaña G, Juárez-Rojas JG, Medina-Urrutia A, Pérez-Hernández N, Rodríguez-Pérez JM, Vargas-Alarcón G, Posadas-Sánchez R. Vitamin D Deficiency is not Associated with Fatty Liver in a Mexican Population. Ann Hepatol 2019; 17:419-425. [PMID: 29735791 DOI: 10.5604/01.3001.0011.7386] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
INTRODUCTION AND AIM Association of vitamin D deficiency (VDD) with fatty liver (FL) disease is controversial. The purpose of this study was to analyze the association of VDD with FL. MATERIAL AND METHODS Cross-sectional study. Data on cardiovascular risk factors, medications, alcohol intake, smoking, diet, and physical activity were obtained. Biochemical, anthropometric, and blood pressure variables were measured. The 25-hydroxyvitamin D (25(OH)D) was quantified through chemoluminescence. The presence of FL, defined as a liver/spleen attenuation index lower than 1.0, was identified through computed axial tomography (CAT). RESULTS The study included 1,467 subjects (49.7% men) with a mean age of 53.3 ± 9.3 years and BMI of 28.3 ± 4.0 kg/m2. Only 11% had optimum values of vitamin D, and 25(OH)D concentration was lower in participants with FL. Multivariate logistic regression models, adjusted for age, gender, BMI, sampling season, glucose, total cholesterol, triglycerides, HOMA-IR, hs-CRP, ALT, AST, and elevated VAT, revealed an association between FL and vitamin D (VD) insufficiency (RM 1.61 [0.99-2.61]) and with VDD (RM 1.68 [1.02-2.77]); however, statistical significance was lost when including caloric consumption and physical activity in the model. CONCLUSIONS In Mexican adults, deficient VD concentration and FL were not independently associated of caloric consumption and physical activity.
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Affiliation(s)
- Fabiola López-Bautista
- Department of Endocrinology. National Institute of Cardiology "Ignacio Chávez", Mexico City, Mexico
| | - Carlos Posadas-Romero
- Department of Endocrinology. National Institute of Cardiology "Ignacio Chávez", Mexico City, Mexico
| | - Luz Y Ruiz-Vargas
- Department of Endocrinology. National Institute of Cardiology "Ignacio Chávez", Mexico City, Mexico
| | | | - Juan G Juárez-Rojas
- Department of Endocrinology. National Institute of Cardiology "Ignacio Chávez", Mexico City, Mexico
| | - Aida Medina-Urrutia
- Department of Endocrinology. National Institute of Cardiology "Ignacio Chávez", Mexico City, Mexico
| | - Nonanzit Pérez-Hernández
- Department of Molecular Biology. National Institute of Cardiology "Ignacio Chávez", Mexico City, Mexico
| | - José M Rodríguez-Pérez
- Department of Molecular Biology. National Institute of Cardiology "Ignacio Chávez", Mexico City, Mexico
| | - Gilberto Vargas-Alarcón
- Department of Molecular Biology. National Institute of Cardiology "Ignacio Chávez", Mexico City, Mexico
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32
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Pacifico L, Osborn JF, Bonci E, Pierimarchi P, Chiesa C. Association between Vitamin D Levels and Nonalcoholic Fatty Liver Disease: Potential Confounding Variables. Mini Rev Med Chem 2019; 19:310-332. [PMID: 30360708 DOI: 10.2174/1389557518666181025153712] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2017] [Revised: 06/16/2017] [Accepted: 08/25/2017] [Indexed: 02/06/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD), historically considered to be the hepatic component of the metabolic syndrome, is a spectrum of fat-associated liver conditions, in the absence of secondary causes, that may progress to nonalcoholic steatohepatitis (NASH), fibrosis, and cirrhosis. Disease progression is closely associated with body weight or fatness, dyslipidemia, insulin resistance, oxidative stress, and inflammation. Recently, vitamin D deficiency has been linked to the pathogenesis and severity of NAFLD because of vitamin D "pleiotropic" functions, with roles in immune modulation, cell differentiation and proliferation, and regulation of inflammation. Indeed, several studies have reported an association between vitamin D and NAFLD/NASH. However, other studies have failed to find an association. Therefore, we sought to critically review the current evidence on the association between vitamin D deficiency and NAFLD/NASH, and to analyze and discuss some key variables that may interfere with this evaluation, such as host-, environment-, and heritability-related factors regulating vitamin D synthesis and metabolism; definitions of deficient or optimal vitamin D status with respect to skeletal and nonskeletal outcomes including NAFLD/NASH; methods of measuring 25(OH)D; and methods of diagnosing NAFLD as well as quantifying adiposity, the cardinal link between vitamin D deficiency and NAFLD.
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Affiliation(s)
- Lucia Pacifico
- Policlinico Umberto I Hospital, Sapienza University of Rome, Viale Regina Elena, 324 00161-Rome, Italy
| | - John F Osborn
- Department of Public Health and Infectious Diseases, Sapienza University of Rome, Viale Regina Elena, 324 00161- Rome, Italy
| | - Enea Bonci
- Department of Experimental Medicine, Sapienza University of Rome, Viale Regina Elena, 324 00161- Rome, Italy
| | - Pasquale Pierimarchi
- Institute of Translational Pharmacology, National Research Council, Via Fosso del Cavaliere, 100 00133- Rome, Italy
| | - Claudio Chiesa
- Institute of Translational Pharmacology, National Research Council, Via Fosso del Cavaliere, 100 00133- Rome, Italy
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33
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Liu S, Liu Y, Wan B, Zhang H, Wu S, Zhu Z, Lin Y, Wang M, Zhang N, Lin S, Zhu Y. Association between Vitamin D Status and Non-Alcoholic Fatty Liver Disease: A Population-Based Study. J Nutr Sci Vitaminol (Tokyo) 2019; 65:303-308. [PMID: 31474679 DOI: 10.3177/jnsv.65.303] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
The relationship between vitamin D levels and non-alcoholic fatty liver disease (NAFLD) remains unestablished. In this study, we aimed to explore the relationship between vitamin D levels and NAFLD based on population survey data. This cross-sectional study was conducted based on data from the National Health and Nutrition Examination Survey. Liver steatosis was diagnosed by ultrasonography. Binary logistic regression analyses were performed to determine the relationship between vitamin D status and NAFLD. A total of 9,782 participants were identified in this analysis, with 46.8% male and an average age of 44.41±0.16 y old. Among them, 6,047 (61.8%) cases were without NAFLD, 1,357 (13.9%) had mild NAFLD, 1,594 (16.3%) had moderate and 784 (8.0%) had severe NAFLD. Compared to those with non-NAFLD or mild NAFLD, patients in the moderate to severe NAFLD group had higher vitamin D deficiency or insufficiency rates (12.4% vs 11.5% and 36.8% vs 33.2%, respectively). After adjustment for male gender, older age, race, BMI, history of diabetes and vitamin D intake, vitamin D levels were independently associated with the severity of NAFLD (vitamin D deficiency group OR: 1.314, 95% CI: 1.129 to 1.529, vitamin D insufficiency group OR: 1.203, 95% CI: 1.090 to 1.328). Besides that, cold season was also found to be an independent factor for NAFLD (OR: 0.896, 95% CI: 0.820 to 0.979). Lower vitamin D level is an independent risk factor for NAFLD. Vitamin D levels are inversely associated with the severity of NAFLD. Cold season increases the risk of NAFLD independently.
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Affiliation(s)
- Shiying Liu
- Liver Research Center, the First Affiliated Hospital of Fujian Medical University
| | - Yuxiu Liu
- Liver Research Center, the First Affiliated Hospital of Fujian Medical University
- The First Clinical Medical Collage of Fujian Medical University
| | - Bo Wan
- Liver Research Center, the First Affiliated Hospital of Fujian Medical University
| | - Haoyang Zhang
- Division of Biostatistics, JC School of Public Health and Primary Care, The Chinese University of Hong Kong
| | - Sumei Wu
- Liver Research Center, the First Affiliated Hospital of Fujian Medical University
- The First Clinical Medical Collage of Fujian Medical University
| | - Zheng Zhu
- Liver Research Center, the First Affiliated Hospital of Fujian Medical University
- The First Clinical Medical Collage of Fujian Medical University
| | - Yanjie Lin
- Liver Research Center, the First Affiliated Hospital of Fujian Medical University
- The First Clinical Medical Collage of Fujian Medical University
| | - Mingfang Wang
- Liver Research Center, the First Affiliated Hospital of Fujian Medical University
| | - Nanwen Zhang
- Department of Pharmacology, School of Pharmacy, Fujian Medical University
| | - Su Lin
- Liver Research Center, the First Affiliated Hospital of Fujian Medical University
| | - Yueyong Zhu
- Liver Research Center, the First Affiliated Hospital of Fujian Medical University
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34
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Wong MCS, Huang JLW, George J, Huang J, Leung C, Eslam M, Chan HLY, Ng SC. The changing epidemiology of liver diseases in the Asia-Pacific region. Nat Rev Gastroenterol Hepatol 2019; 16:57-73. [PMID: 30158570 DOI: 10.1038/s41575-018-0055-0] [Citation(s) in RCA: 233] [Impact Index Per Article: 38.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
This Review presents current epidemiological trends of the most common liver diseases in Asia-Pacific countries. Hepatitis B virus (HBV) remains the primary cause of cirrhosis; despite declining prevalence in most Asian nations, this virus still poses a severe threat in some territories and regions. Mortality resulting from HBV infection is declining as a result of preventive measures and antiviral treatments. The epidemiological transition of hepatitis C virus (HCV) infection has varied in the region in the past few decades, but the medical burden of infection and the prevalence of its related cancers are increasing. The lack of licensed HCV vaccines highlights the need for novel treatment strategies. The prevalence of nonalcoholic fatty liver disease (NAFLD) has risen in the past decade, mostly owing to increasingly urbanized lifestyles and dietary changes. Alternative herbal medicine and dietary supplements are major causes of drug-induced liver injury (DILI) in some countries. Complications arising from these chronic liver diseases, including cirrhosis and liver cancer, are therefore emerging threats in the Asia-Pacific region. Key strategies to control these liver diseases include monitoring of at-risk populations, implementation of national guidelines and increasing public and physician awareness, in concert with improving access to health care.
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Affiliation(s)
- Martin C S Wong
- Institute of Digestive Disease, Faculty of Medicine, The Chinese University of Hong Kong, Sha Tin, Hong Kong
- State Key Laboratory for Digestive Disease, Faculty of Medicine, The Chinese University of Hong Kong, Sha Tin, Hong Kong
- J.C. School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Sha Tin, Hong Kong
- Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Sha Tin, Hong Kong
| | - Jason L W Huang
- J.C. School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Sha Tin, Hong Kong
| | - Jacob George
- Storr Liver Centre, Westmead Millennium Institute and Westmead Hospital, University of Sydney, Sydney, New South Wales, Australia
| | - Junjie Huang
- J.C. School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Sha Tin, Hong Kong
| | - Colette Leung
- J.C. School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Sha Tin, Hong Kong
| | - Mohammed Eslam
- Storr Liver Centre, Westmead Millennium Institute and Westmead Hospital, University of Sydney, Sydney, New South Wales, Australia
| | - Henry L Y Chan
- Institute of Digestive Disease, Faculty of Medicine, The Chinese University of Hong Kong, Sha Tin, Hong Kong
- State Key Laboratory for Digestive Disease, Faculty of Medicine, The Chinese University of Hong Kong, Sha Tin, Hong Kong
- Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Sha Tin, Hong Kong
| | - Siew C Ng
- Institute of Digestive Disease, Faculty of Medicine, The Chinese University of Hong Kong, Sha Tin, Hong Kong.
- State Key Laboratory for Digestive Disease, Faculty of Medicine, The Chinese University of Hong Kong, Sha Tin, Hong Kong.
- Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Sha Tin, Hong Kong.
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35
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Luo J, Chen Q, Shen T, Wang X, Fang W, Wu X, Yuan Z, Chen G, Ling W, Chen Y. Association of sex hormone-binding globulin with nonalcoholic fatty liver disease in Chinese adults. Nutr Metab (Lond) 2018; 15:79. [PMID: 30455723 PMCID: PMC6225668 DOI: 10.1186/s12986-018-0313-8] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2018] [Accepted: 10/15/2018] [Indexed: 02/07/2023] Open
Abstract
Background Sex hormone-binding globulin (SHBG), a glycoprotein synthesized by hepatocytes, has been linked to insulin resistance and hepatic lipid metabolism and is suggested to be associated with nonalcoholic fatty liver disease (NAFLD). This study aimed to investigate the association of SHBG with NAFLD in Chinese adults. Methods We conducted a community-based, cross-sectional study in China involving 2912 participants aged 40–75 years old. All participants underwent detection for hepatic fat infiltration by ultrasound in addition to providing complete medical history and undergoing physical and blood biochemical examinations. The association of serum SHBG with the presence of NAFLD was reported by adjusted odds ratio after applying logistic regression models. To further explore the relationship between SHBG and NAFLD, mRNA expression of SHBG and hepatocyte nuclear factor 4-α (HNF4α), as well as intrahepatic triglycerides, were determined from the liver tissues of 32 subjects with different degrees of steatosis. Results Serum SHBG levels in patients with NAFLD (median, 43.8 nmol/L; interquartile range, 33.4–56.8 nmol/L) were significantly lower than those in non-NAFLD subjects (median, 63.4 nmol/L; interquartile range, 47.6–83.1 nmol/L). Serum SHBG levels were inversely correlated with WHR, trunk fat percentage, glucose, HOMA-IR, TG, UA and DHEAS, and were positively correlated with HDL-C levels (all p < 0.001). Logistic regression analysis indicated that serum SHBG levels were negatively associated with the presence of NAFLD in all subjects, as well as the subgroups stratified by sex, BMI and HOMA-IR (all p < 0.05). In human liver tissues, SHBG and HNF4α mRNA expression decreased along with the elevated grade of hepatic steatosis. Both SHBG and HNF4α mRNA expression levels were negatively correlated with intrahepatic triglycerides. Conclusions These results demonstrate that SHBG levels were negatively associated with the presence of NAFLD in middle-aged and elderly Chinese adults. Electronic supplementary material The online version of this article (10.1186/s12986-018-0313-8) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Jing Luo
- 1Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou, 510080 China.,2Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou, 510080 China
| | - Qian Chen
- 1Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou, 510080 China.,2Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou, 510080 China.,5Department of Cardiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120 China
| | - Tianran Shen
- 1Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou, 510080 China.,2Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou, 510080 China
| | - Xu Wang
- 1Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou, 510080 China.,2Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou, 510080 China
| | - Wanjun Fang
- 1Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou, 510080 China.,2Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou, 510080 China
| | - Xiaocai Wu
- 4Department of Hepatic Surgery,The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510630 China
| | - Zenan Yuan
- 4Department of Hepatic Surgery,The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510630 China
| | - Gengdong Chen
- 2Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou, 510080 China.,3Department of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou, 510080 China
| | - Wenhua Ling
- 1Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou, 510080 China.,2Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou, 510080 China
| | - Yuming Chen
- 2Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou, 510080 China.,3Department of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou, 510080 China
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36
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Cigarette Smoke During Breastfeeding in Rats Changes Glucocorticoid and Vitamin D Status in Obese Adult Offspring. Int J Mol Sci 2018; 19:ijms19103084. [PMID: 30304827 PMCID: PMC6213898 DOI: 10.3390/ijms19103084] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2018] [Revised: 09/28/2018] [Accepted: 10/05/2018] [Indexed: 12/11/2022] Open
Abstract
Maternal smoking increases obesogenesis in the progeny. Obesity is associated with several hormonal dysfunctions. In a rat model of postnatal tobacco smoke exposure, we previously reported increased central fat depot and disruption of some hormonal systems in the adult offspring. As both glucocorticoids and vitamin D alter lipogenesis and adipogenesis, here we evaluated the metabolism of these two hormones in visceral adipose tissue (VAT) and liver by Western blotting, and possible associations with lipogenesis biomarkers in adult rats that were exposed to tobacco smoke during their suckling period. At postnatal day (PN) 3, dams and offspring of both sexes were exposed (S group) or not (C group) to tobacco smoke, 4 × 1 h/day. At PN180, corticosteronemia was lower in S male and higher in S female offspring, without alterations in peripheral glucocorticoid metabolism and receptor. Adrenal ACTH receptor (MC2R) was higher in both sexes of S group. Despite unchanged serum vitamin D, liver 25-hydroxylase was higher in both sexes of S group. Male S offspring had higher 1α-hydroxylase, acetyl-CoA carboxylase (ACC), and fatty acid synthase (FAS) in VAT. Both sexes showed increased ACC protein content and reduced sirtuin mRNA in liver. Male S offspring had lower liver peroxisome proliferator-activated receptor-α. Tobacco exposure during lactation induced abdominal obesity in both sexes via distinct mechanisms. Males and females seem to develop HPA-axis dysfunction instead of changes in glucocorticoid metabolism and action. Lipogenesis in VAT and liver, as well as vitamin D status, are more influenced by postnatal smoke exposure in male than in female adult rat offspring.
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37
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Chen HJ, Yang HY, Hsueh KC, Shen CC, Chen RY, Yu HC, Wang TL. Increased risk of osteoporosis in patients with nonalcoholic fatty liver disease: A population-based retrospective cohort study. Medicine (Baltimore) 2018; 97:e12835. [PMID: 30334985 PMCID: PMC6211874 DOI: 10.1097/md.0000000000012835] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
The study aims to investigate the association between nonalcoholic fatty liver disease (NAFLD) and osteoporosis.We employed a retrospective cohort study design using the National Health Insurance Research Database in Taiwan. Our study included 2 cohorts: 4318 patients with NAFLD and 17,272 patients without NAFLD for comparison. They were matched by sex and age on the date of enrollment between January 1, 2000 and December 31, 2003. The study population in both groups was observed from the enrollment date until December 31, 2013. The incidence and the risk ratios of subsequent osteoporosis were calculated separately in both cohorts. A Cox proportional hazards model was used to assess the potential confounding variables of NAFLD on the pathogenesis of osteoporosis.The eligible study participants comprised 4318 patients in the NAFLD and 17,272 in control cohorts. The median follow-up duration was 10.7 and 10.83 years in the NAFLD and control groups, respectively. The risk of new-onset osteoporosis was higher in patients with NAFLD than in the comparison cohort. In addition, the difference of the incidence of new-onset osteoporosis remained significant among the 2 cohorts in the follow-up durations of within 1 year and more than 10 years. Patients with NAFLD were 1.35 times more likely to develop subsequent osteoporosis compared with those without NAFLD (95% confidence interval = 1.20-1.53).Our finding indicates that NAFLD might increase the risk of developing new-onset osteoporosis. For earlier detection and intervention, screening for osteoporosis in patients with the NAFLD, especially those with lower income and co-morbid with diabetes mellitus and chronic obstructive pulmonary disease, may be recommended.
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Affiliation(s)
- Hon-Jhe Chen
- Department of Family Medicine, Kaohsiung Veterans General Hospital, Kaohsiung
| | - Hao-Yu Yang
- Department of Family Medicine, Kaohsiung Veterans General Hospital, Kaohsiung
| | - Kuang-Chieh Hsueh
- Department of Family Medicine, Kaohsiung Veterans General Hospital, Kaohsiung
| | - Cheng-Che Shen
- Department of Psychiatry, Chiayi Branch, Taichung Veterans General Hospital, Chiayi
- School of Medicine, National Yang-Ming University
| | - Ru-Yi Chen
- Department of Family Medicine, Kaohsiung Veterans General Hospital, Kaohsiung
| | - Hsien-Chung Yu
- Division of Gastroenterology and General Medicine, Department of Medicine, Kaohsiung Veterans General Hospital, Kaohsiung
| | - Tzu-Lin Wang
- Division of Cardiology, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital
- Institute of Emergency and Critical Care Medicine, National Yang-Ming University, Taipei, Taiwan
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38
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Sun SM, Wang YY, Zhang Q, Liu L, Meng G, Yao ZX, Wu HM, Xia Y, Bao X, Gu YQ, Wang HL, Shi HB, Xu HY, Wang X, Zhou M, Jiao HL, Jia QY, Wang BM, Niu KJ. Serum levels of immunoglobulins in an adult population and their relationship with nonalcoholic fatty liver disease. J Dig Dis 2018; 19:498-507. [PMID: 29989347 DOI: 10.1111/1751-2980.12646] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2017] [Revised: 06/23/2018] [Accepted: 07/05/2018] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Few studies have reported the association between nonalcoholic fatty liver disease (NAFLD) and immunoglobulins. In this study, we aimed to investigate the relationship between serum immunoglobulin levels and NAFLD in a Chinese adult population. METHODS We performed a cross-sectional study including 11 261 Chinese adults. NAFLD was diagnosed based on the Chinese Guidelines for the diagnosis and treatment of fatty liver diseases and an alcohol intake of <70 g/week in women and <140 g/week in men, and serum immunoglobulin (Ig) levels were determined using immune nephelometry. Multiple logistic regression analysis was done to assess relationships between concentrations of serum immunoglobulins and NAFLD. RESULTS Of the 11 261 adults recruited from January 2010 to December 2015, the prevalence of NAFLD was 40.8% (n = 4598). The geometric mean levels of IgG, IgM, IgE and IgA were 1177.49 mg/dL (95% confidence interval [CI] 1173.07-1181.93), 93.56 mg/dL (95% CI 92.70-94.42), 30.70 IU/mL (95% CI 29.92-31.49) and 216.64 mg/dL (95% CI 214.95-218.34), respectively. Compared with the lowest quintile, the multivariable adjusted odds ratio (95% CI) of NAFLD for the highest quintile of IgG, IgM, IgE, and IgA were 0.78 (0.66-0.92), 0.71 (0.60-0.84), 0.98 (0.84-1.15) and 1.41 (1.21-1.66), respectively. CONCLUSION Increased IgA and decreased IgG and IgM levels are independently associated with NAFLD prevalence. Further research is needed to explore the causal association between serum immunoglobulins and NAFLD.
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Affiliation(s)
- Shao Mei Sun
- Health Management Center, Tianjin Medical University General Hospital, Tianjin, China
| | - Yan Yan Wang
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, China
| | - Qing Zhang
- Health Management Center, Tianjin Medical University General Hospital, Tianjin, China
| | - Li Liu
- Health Management Center, Tianjin Medical University General Hospital, Tianjin, China
| | - Ge Meng
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, China
| | - Zhan Xin Yao
- Tianjin Institute of Health and Environmental Medicine, Tianjin, China
| | - Hong Mei Wu
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, China
| | - Yang Xia
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, China
| | - Xue Bao
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, China
| | - Ye Qing Gu
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, China
| | - Hong Lei Wang
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, China
| | - Hong Bin Shi
- Health Management Center, Tianjin Medical University General Hospital, Tianjin, China
| | - Hai Yan Xu
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, China
| | - Xing Wang
- Health Management Center, Tianjin Medical University General Hospital, Tianjin, China
| | - Ming Zhou
- Health Management Center, Tianjin Medical University General Hospital, Tianjin, China
| | - Huan Li Jiao
- Health Management Center, Tianjin Medical University General Hospital, Tianjin, China.,Department of Gastroenterology, Tianjin Medical University General Hospital, Tianjin, China
| | - Qi Yu Jia
- Health Management Center, Tianjin Medical University General Hospital, Tianjin, China
| | - Bang Mao Wang
- Department of Gastroenterology, Tianjin Medical University General Hospital, Tianjin, China
| | - Kai Jun Niu
- Health Management Center, Tianjin Medical University General Hospital, Tianjin, China.,Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, China
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Yu J, Yang X, Yang X, Yang M, Wang P, Yang Y, Yang J, Li W, Xu J. Nonylphenol aggravates non-alcoholic fatty liver disease in high sucrose-high fat diet-treated rats. Sci Rep 2018; 8:3232. [PMID: 29459774 PMCID: PMC5818617 DOI: 10.1038/s41598-018-21725-y] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2017] [Accepted: 02/05/2018] [Indexed: 12/19/2022] Open
Abstract
Exposure to environmental endocrine disruptors (EEDs) contributes to the pathogenesis of many metabolic disorders. Here, we have analyzed the effect of the EED-nonylphenol (NP) on the promotion of non-alcoholic fatty liver disease (NAFLD) in rats fed high sucrose-high fat diet (HSHFD). Fifty Sprague-Dawley rats were divided into five groups: controls fed a normal diet (C-ND); HSHFD-fed controls (C-HSHFD); and rats fed a HSHFD combined with NP at doses of 0.02 μg/kg/day (NP-L-HSHFD), 0.2 μg/kg/day (NP-M-HSHFD), and 2 μg/kg/day (NP-H-HSHFD). Subchronic exposure to NP coupled with HSHFD increased daily water and food intake (p < 0.05), hepatic echogenicity and oblique liver diameter (p < 0.05), and plasma levels of alanine aminotransferase, aspartate aminotransferase, total cholesterol, triglycerides, and low density lipoprotein cholesterol (p < 0.05). Combined exposure to NP and HSHFD induced macrovesicular steatosis with dilation and congestion of the central vein, liver inflammatory cell infiltration, and expression of genes regulating lipid metabolism, SREBP-1C, FAS, and Ucp2. These results demonstrate that NP aggravates NAFLD in HSHFD-treated rats by up-regulating lipogenic genes, and that HSHFD increases the toxic effects of NP. Thus subchronic NP exposure may lead to NAFLD, especially when combined with a high-sucrose/high-fat diet.
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Affiliation(s)
- Jie Yu
- School of Public Health, Zunyi Medical University, Zunyi, Guizhou, 563003, P.R. China
| | - Xuesong Yang
- Department of Hospital Infection and Control, The First People's Hospital of Guiyang city, Guiyang, Guizhou, 550002, P.R. China
| | - Xuefeng Yang
- Department of Gastrointestinal Surgery, The Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, 563003, P.R. China
| | - Mengxue Yang
- Department of Endocrinology, The Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, 563099, P.R. China
| | - Pan Wang
- Department of Nuclear Medicine, The Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, 563099, P.R. China
| | - Yu Yang
- School of Public Health, Zunyi Medical University, Zunyi, Guizhou, 563003, P.R. China
| | - Jing Yang
- School of Public Health, Zunyi Medical University, Zunyi, Guizhou, 563003, P.R. China
| | - Wenmei Li
- School of Public Health, Zunyi Medical University, Zunyi, Guizhou, 563003, P.R. China
| | - Jie Xu
- School of Public Health, Zunyi Medical University, Zunyi, Guizhou, 563003, P.R. China.
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40
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Wang N, Chen C, Zhao L, Chen Y, Han B, Xia F, Cheng J, Li Q, Lu Y. Vitamin D and Nonalcoholic Fatty Liver Disease: Bi-directional Mendelian Randomization Analysis. EBioMedicine 2018; 28:187-193. [PMID: 29339098 PMCID: PMC5835542 DOI: 10.1016/j.ebiom.2017.12.027] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2017] [Revised: 12/20/2017] [Accepted: 12/22/2017] [Indexed: 12/26/2022] Open
Abstract
Background Vitamin D deficiency is associated with nonalcoholic fatty liver disease (NAFLD) in many cross-sectional studies. However, the causality between them has not been established. We used bi-directional mendelian randomization (MR) analysis to explore the causal relationship between 25-hydroxyvitamin D [25(OH)D] and NAFLD. Methods 9182 participants were included from a survey in East China from 2014 to 2016. We calculated weighted genetic risk scores (GRS) for 25(OH)D concentration and NAFLD based on 25(OH)D-related and NAFLD-related single nucleotide polymorphisms. Presence of liver steatosis was assessed using ultrasound. Instrumental variable was used to measure the causal relationship between them. Results An SD increase in the 25(OH)D GRS was significantly associated with 25(OH)D (β 1.29, 95%CI − 1.54, − 1.04, P < 0.05) but not with NAFLD (OR 0.97, 95%CI 0.92, 1.01). An SD increase in NAFLD GRS was also strongly associated with NAFLD (OR 1.09, 95%CI 1.04, 1.15, P < 0.05) but not with 25(OH)D (β − 0.15, 95%CI − 0.41, 0.10). Using an instrumental variable estimator, no associations were found for genetically instrumented 25(OH)D with NAFLD and for genetically instrumented NAFLD with 25(OH)D. Conclusion Our results support the conclusion that there is no causal association between vitamin D and NAFLD using a bi-directional MR approach in a Chinese population.
The causality between vitamin D and NAFLD was controversial in human beings. Using mendelian randomization analysis, 25(OH)D and NAFLD are not causally associated. Long-term vitamin D deficiency may not affect the development of NAFLD.
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Affiliation(s)
- Ningjian Wang
- Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China
| | - Chi Chen
- Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China
| | - Li Zhao
- Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China
| | - Yi Chen
- Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China
| | - Bing Han
- Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China
| | - Fangzhen Xia
- Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China
| | - Jing Cheng
- Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China
| | - Qin Li
- Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China
| | - Yingli Lu
- Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China.
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41
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Sharifi N, Amani R. Vitamin D supplementation and non-alcoholic fatty liver disease: A critical and systematic review of clinical trials. Crit Rev Food Sci Nutr 2017; 59:693-703. [PMID: 29035092 DOI: 10.1080/10408398.2017.1389693] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Previous observational studies have found a relationship between vitamin D deficiency and non-alcoholic fatty liver disease (NAFLD). However, this type of study could not show the causal relationship between these two conditions. Therefore, we systematically and critically reviewed the available clinical trials to elucidate such relationship. We searched databases such as Medline, Scopus and Cochrane to identify the clinical trials that assessed the effects of vitamin D supplementation in adults with NAFLD. The outcome variables of interest were indicators of hepatic steatosis, liver enzymes, insulin resistance, inflammation and oxidative stress. A total of 6 studies were included in the qualitative analysis. Only in two studies the grade of hepatic steatosis decreased significantly after vitamin D supplementation. The changes in insulin resistance parameters were reported significant only in one. Of the 3 included studies that measured biomarkers of inflammation and oxidative stress, one revealed a significant decrease in these biomarkers after vitamin D supplementation. Findings from current review study provided new insight into the factors that could affect the therapeutic role of vitamin D in NAFLD. Factors such as gender differences, baseline serum status of vitamin D, co-supplementation with calcium and gene polymorphism should be considered when designing future clinical trials.
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Affiliation(s)
- Nasrin Sharifi
- a Research Center for Biochemistry and Nutrition in Metabolic Diseases , Kashan University of Medical Sciences , Kashan , Iran
| | - Reza Amani
- b Food Security Research Center, Department of Clinical Nutrition , School of Nutrition and Food Science, Isfahan University of Medical Sciences , Isfahan , Iran
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Drori A, Rotnemer-Golinkin D, Avni S, Drori A, Danay O, Levanon D, Tam J, Zolotarev L, Ilan Y. Attenuating the rate of total body fat accumulation and alleviating liver damage by oral administration of vitamin D-enriched edible mushrooms in a diet-induced obesity murine model is mediated by an anti-inflammatory paradigm shift. BMC Gastroenterol 2017; 17:130. [PMID: 29179679 PMCID: PMC5704499 DOI: 10.1186/s12876-017-0688-4] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2017] [Accepted: 11/17/2017] [Indexed: 02/08/2023] Open
Abstract
Background Hypovitaminosis D is associated with many features of the metabolic syndrome, including non-alcoholic fatty liver disease. Vitamin D-enriched mushrooms extracts exert a synergistic anti-inflammatory effect. The aim of the present study is to determine the immunomodulatory effect of oral administration of vitamin D-enriched mushrooms extracts on high-fat diet (HFD) animal model of non-alcoholic steatohepatitis (NASH). Methods C57BL/6 mice on HFD were orally administered with vitamin D supplement, Lentinula edodes (LE) mushrooms extract, or vitamin D-enriched mushrooms extract for 25 weeks. Mice were studied for the effect of the treatment on the immune system, liver functions and histology, insulin resistance and lipid profile. Results Treatment with vitamin D-enriched LE extracts was associated with significant attenuation of the rate of total body fat accumulation, along with a decrease in hepatic fat content as measured by an EchoMRI. Significant alleviation of liver damage manifested by a marked decrease in ALT, and AST serum levels (from 900 and 1021 U/L in the control group to 313 and 340; 294 and 292; and 366 and 321 U/L for ALT and AST, in Vit D, LE and LE + Vit D treated groups, respectively). A corresponding effect on hepatocyte ballooning were also noted. A significant decrease in serum triglycerides (from 103 to 75, 69 and 72 mg/dL), total cholesterol (from 267 to 160, 157 and 184 mg/dL), and LDL cholesterol (from 193 mg/dL to 133, 115 and 124 mg/dL) along with an increase in the HDL/LDL ratio, and improved glucose levels were documented. These beneficial effects were associated with a systemic immunomodulatory effect associated with an increased CD4/CD8 lymphocyte ratio (from 1.38 in the control group to 1.69, 1.71 and 1.63), and a pro- to an anti-inflammatory cytokine shift. Conclusions Oral administration of vitamin-D enriched mushrooms extracts exerts an immune modulatory hepato-protective effect in NASH model.
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Affiliation(s)
- A Drori
- Gastroenterology and Liver Units, Department of Medicine, Hadassah-Hebrew University Medical Center, P.O.B 12000, -91120, Jerusalem, IL, Israel
| | - D Rotnemer-Golinkin
- Gastroenterology and Liver Units, Department of Medicine, Hadassah-Hebrew University Medical Center, P.O.B 12000, -91120, Jerusalem, IL, Israel
| | - S Avni
- Migal, Galilee Research Institute, Kiryat Shmona, Israel
| | - A Drori
- Obesity and Metabolism Laboratory, The Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel
| | - O Danay
- Migal, Galilee Research Institute, Kiryat Shmona, Israel
| | - D Levanon
- Migal, Galilee Research Institute, Kiryat Shmona, Israel
| | - J Tam
- Obesity and Metabolism Laboratory, The Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel
| | - L Zolotarev
- Gastroenterology and Liver Units, Department of Medicine, Hadassah-Hebrew University Medical Center, P.O.B 12000, -91120, Jerusalem, IL, Israel
| | - Y Ilan
- Gastroenterology and Liver Units, Department of Medicine, Hadassah-Hebrew University Medical Center, P.O.B 12000, -91120, Jerusalem, IL, Israel.
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Lu Y, Zheng Y, Wang N, Chen Y, Li Q, Han B, Chen Y, Cheng J, Zhai H, Xia F, Meng Y, Lu Y. The Relationship between Vitamin D and Type 2 Diabetes Is Intriguing: Glimpses from the Spect-China Study. ANNALS OF NUTRITION AND METABOLISM 2017; 71:195-202. [PMID: 29024934 DOI: 10.1159/000480711] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/21/2017] [Accepted: 08/24/2017] [Indexed: 12/15/2022]
Abstract
OBJECTIVE Vitamin D is a multifunctional vitamin for our body. Type 2 diabetes mellitus (T2DM) is a common metabolic disease. Whether T2DM affects the serum 25(OH)D level has not been reported. The objective of this study was to reveal the extent to which vitamin D is present in the population in East China and to explore the relationship between serum 25(OH)D and T2DM. METHODS The cohort was selected based on a large investigation named Survey on Prevalence in East China including 12,702 participants aged 21-92 years old. All the participants completed the questionnaire and went through a physical examination. Fasting blood samples were collected to test serum 25(OH)D and other metabolism-related indicators. AVONA was used to test the significance of differences among groups. Multinomial logistic regression was used to assess the association of T2DM with serum 25(OH)D level. RESULTS The overall percentage of vitamin D deficiency was 80.55% (male 74.1%, female 85.0%). Men with lower serum 25(OH)D level had high value in homeostasis model assessment of insulin resistance and HbA1c. The serum 25(OH)D level of those who were diagnosed with T2DM was higher than that in non-diabetics. The serum 25(OH)D level of pre-diabetes was the highest. T2DM patients trended to have higher serum 25(OH)D levels. CONCLUSION Vitamin D deficiency is common among the people in East-China. T2DM patients had higher levels of serum 25(OH)D. The relationship between vitamin D and T2DM is intriguing. It seemed that vitamin D was either irrelevant directly to T2DM or resisted in T2DM patients.
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Affiliation(s)
- You Lu
- Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China
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Fan JG, Kim SU, Wong VWS. New trends on obesity and NAFLD in Asia. J Hepatol 2017; 67:862-873. [PMID: 28642059 DOI: 10.1016/j.jhep.2017.06.003] [Citation(s) in RCA: 789] [Impact Index Per Article: 98.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2017] [Revised: 05/31/2017] [Accepted: 06/07/2017] [Indexed: 12/12/2022]
Abstract
Traditionally, obesity and its related diseases have been considered a problem in Western countries. However, in the past two decades, urbanisation in many Asian countries has led to a sedentary lifestyle and overnutrition, setting the stage for the epidemic of obesity. This article reviews the epidemiological trend of obesity in Asia, with special emphasis on the emerging condition of non-alcoholic fatty liver disease (NAFLD). Currently, the population prevalence of NAFLD in Asia is around 25%, like many Western countries. While hepatocellular carcinoma and end-stage liver disease secondary to NAFLD remain uncommon, a rising trend has emerged. Around 8-19% of Asians with body mass indexes less than 25kg/m2 are also found to have NAFLD, a condition often described as "lean" or "non-obese" NAFLD. Although this condition is generally less severe than that in more obese patients, steatohepatitis and fibrotic disease are well recognized. Central adiposity, insulin resistance and weight gain are major risk factors, and genetic predisposition, such as the PNPLA3 polymorphism appears to be more important in the development of NAFLD in the non-obese population. Lifestyle modification remains the cornerstone of management for obesity and NAFLD, but few patients can achieve adequate weight reduction and even fewer can maintain the weight in the long run. While pharmacological agents have entered phase III development for steatohepatitis, Asian patients are under-represented in most drug trials. Future studies should define the optimal management of obesity and NAFLD in Asia.
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Affiliation(s)
- Jian-Gao Fan
- Center for Fatty Liver, Department of Gastroenterology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
| | - Seung-Up Kim
- Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, South Korea
| | - Vincent Wai-Sun Wong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China; State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China.
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45
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Hu J, Li P, Song Y, Ge YX, Meng XM, Huang C, Li J, Xu T. Progress and prospects of circular RNAs in Hepatocellular carcinoma: Novel insights into their function. J Cell Physiol 2017; 233:4408-4422. [PMID: 28833094 DOI: 10.1002/jcp.26154] [Citation(s) in RCA: 43] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2017] [Revised: 08/10/2017] [Accepted: 08/11/2017] [Indexed: 12/13/2022]
Abstract
Hepatocellular carcinoma (HCC) is one of the most predominant subjects of liver malignancies, which arouses global concern in the recent years. Advanced studies have found that Circular RNAs (circRNAs) are differentially expressed in HCC, with its regulatory capacity in HCC pathogenesis and metastasis. However, the underlying mechanism remains largely unknown. In this review, we summarized the functions and mechanisms of those aberrantly expressed circRNAs in HCC tissues. We hope to enlighten more comprehensive studies on the detailed mechanisms of circRNAs and explore their potential values in clinic applications. It revealed that hsa_circ_0004018 can be used as a potential biomarker in HCC diagnosis, with its superior sensitivity to alpha-fetoprotein (AFP). Notably, the correlation of circRNA abundance in the proliferation of liver regeneration (LR) has recently been clarified and different circRNA profiles served as candidates for nonalcoholic steatohepatitis (NASH) diagnosis also be discussed. Therefore, the improved understanding of circRNAs in HCC pathogenesis and metastasis proposed a novel basis for the early diagnosis in HCC patients, which provides a useful resource to explore the pathogenesis of HCC.
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Affiliation(s)
- Ji Hu
- School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei, China.,Institute for Liver Diseases of Anhui Medical University, Anhui Medical University, Hefei, China
| | - Peng Li
- Department of Medical, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Yang Song
- Department of Pain treatment, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Yun-Xuan Ge
- Beijing Institute of Radiation Medicine, Academy of Military Medical Sciences, Beijing, China
| | - Xiao-Ming Meng
- School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei, China.,Institute for Liver Diseases of Anhui Medical University, Anhui Medical University, Hefei, China
| | - Cheng Huang
- School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei, China.,Institute for Liver Diseases of Anhui Medical University, Anhui Medical University, Hefei, China
| | - Jun Li
- School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei, China.,Institute for Liver Diseases of Anhui Medical University, Anhui Medical University, Hefei, China
| | - Tao Xu
- School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei, China.,Institute for Liver Diseases of Anhui Medical University, Anhui Medical University, Hefei, China
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Barchetta I, Cimini FA, Cavallo MG. Vitamin D Supplementation and Non-Alcoholic Fatty Liver Disease: Present and Future. Nutrients 2017; 9:nu9091015. [PMID: 28906453 PMCID: PMC5622775 DOI: 10.3390/nu9091015] [Citation(s) in RCA: 52] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2017] [Revised: 09/04/2017] [Accepted: 09/11/2017] [Indexed: 12/14/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic hepatic disease throughout the Western world and is recognized as the main cause of cryptogenic cirrhosis; however, the identification of an effective therapy for NAFLD is still a major challenge. Vitamin D deficiency is a wide-spread condition which reaches epidemic proportions in industrialized countries, mainly in relation to current lifestyle and limited dietary sources. Epidemiological studies point towards an association between hypovitaminosis D and the presence of NAFLD and steatohepatitis (NASH), independently of confounders such as obesity and insulin resistance. Furthermore, several pieces of experimental data have shown the anti-fibrotic, anti-inflammatory and insulin-sensitizing properties exerted by vitamin D on hepatic cells. However, results from trials evaluating the effects of oral vitamin D supplementation on liver damage in NAFLD and NASH are controversial. The aim of this review is to give an overview of the evidence currently available from clinical trials and to discuss possible shortcomings and new strategies to be considered in future investigations.
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Affiliation(s)
- Ilaria Barchetta
- Department of Experimental Medicine, Section of Medical Pathophysiology, Food Science and Endocrinology, Sapienza University of Rome, Rome 00161, Italy.
| | - Flavia Agata Cimini
- Department of Experimental Medicine, Section of Medical Pathophysiology, Food Science and Endocrinology, Sapienza University of Rome, Rome 00161, Italy.
| | - Maria Gisella Cavallo
- Department of Experimental Medicine, Section of Medical Pathophysiology, Food Science and Endocrinology, Sapienza University of Rome, Rome 00161, Italy.
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Ha Y, Hwang SG, Rim KS. The Association between Vitamin D Insufficiency and Nonalcoholic Fatty Liver Disease: A Population-Based Study. Nutrients 2017; 9:nu9080806. [PMID: 28749418 PMCID: PMC5579600 DOI: 10.3390/nu9080806] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2017] [Revised: 07/14/2017] [Accepted: 07/20/2017] [Indexed: 12/18/2022] Open
Abstract
Previous studies have shown inconsistent results regarding the association between vitamin D insufficiency and nonalcoholic fatty liver disease (NAFLD). We attempted to demonstrate this relationship using population-based data. Vitamin D insufficiency was defined as a 25(OH)D level ≤20 ng/mL. Hepatic steatosis index was calculated to define NAFLD. Significant fibrosis was assessed using Body mass index, AST/ALT Ratio, Diabetes (BARD) score. Logistic regression analyses were performed to determine the relationship between vitamin D insufficiency and NAFLD. Among 1812 participants, 409 (22.6%) had NAFLD. Patients with nonalcoholic fatty liver disease were more likely to be male (56.7%), had higher body mass index (28.1 kg/m²), and had more metabolic syndrome (57.2%). The proportion of vitamin D insufficiency did not differ between NAFLD and non-NAFLD (77.5% vs. 77.4%). Logistic regression analyses showed that BMI, diabetes, and triglyceride level were significantly associated with NAFLD, whereas vitamin D insufficiency was not related. Subgroup analyses involving non-obese participants, male participants, and participants without metabolic syndrome showed similar results. The BARD score and the proportion of significant fibrosis by BARD score did not differ according to vitamin D status. Vitamin D insufficiency was not associated with the presence of NAFLD as assessed by validated noninvasive prediction models.
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Affiliation(s)
- Yeonjung Ha
- Department of Hepatology, CHA Bundang Medical Center, CHA University, Seongnam-si 13496, Gyeonggi-do, Korea.
| | - Seong Gyu Hwang
- Department of Hepatology, CHA Bundang Medical Center, CHA University, Seongnam-si 13496, Gyeonggi-do, Korea.
| | - Kyu Sung Rim
- Department of Hepatology, CHA Bundang Medical Center, CHA University, Seongnam-si 13496, Gyeonggi-do, Korea.
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48
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Lu Y, Wang N, Chen Y, Nie X, Li Q, Han B, Chen Y, Xia F, Cang Z, Lu M, Meng Y, Lu Y. Health-related quality of life in type-2 diabetes patients: a cross-sectional study in East China. BMC Endocr Disord 2017; 17:38. [PMID: 28683734 PMCID: PMC5501343 DOI: 10.1186/s12902-017-0187-1] [Citation(s) in RCA: 35] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2017] [Accepted: 06/27/2017] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND Used the EuroQoL-5 dimension (EQ-5D) to evaluate the health status of 5310 residents who live in East China, and compared the health-related quality of life (HRQoL) with 311 patients with type 2 diabetes as well as to explore the main influence factors to HRQoL in East China. METHODS The cohort includes 5310 participants aged 18-89 years old lived in East China. EuroQoL-5 dimension (EQ-5D) scale was used for the assessment of health-related quality of life. RESULTS The mean age of the cohort was 52.2 ± 13.4 years of which 43.7% were male. A moderate level of health-related quality of life was measured of that EQ-5D index and EQ-VAS scores were 0.939 ± 0.111 and 80.06 ± 11.58, respectively. There was a significant difference between diabetes patients and non-diabetes (p = 0.029, p < 0.001, respectively). The age had an inverse correlation with the EQ-5D scores both in general population and diabetes patients. The EQ-5D Vas was weakly adversely associated with the FPG, HbA1c and HOMA-IR. CONCLUSION The overall health-related quality of life of population in East-China was moderate. Diabetes patients had lower score of health-related quality. The healthy-related quality was associated with the age, gender, economic development of region, level of education and marital status.
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Affiliation(s)
- You Lu
- Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, 200011 China
| | - Ningjian Wang
- Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, 200011 China
| | - Yi Chen
- Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, 200011 China
| | - Xiaomin Nie
- Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, 200011 China
| | - Qin Li
- Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, 200011 China
| | - Bing Han
- Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, 200011 China
| | - Yingchao Chen
- Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, 200011 China
| | - Fangzhen Xia
- Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, 200011 China
| | - Zhen Cang
- Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, 200011 China
| | - Meng Lu
- Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, 200011 China
| | - Ying Meng
- Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, 200011 China
| | - Yingli Lu
- Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, 200011 China
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Cimini FA, Barchetta I, Carotti S, Bertoccini L, Baroni MG, Vespasiani-Gentilucci U, Cavallo MG, Morini S. Relationship between adipose tissue dysfunction, vitamin D deficiency and the pathogenesis of non-alcoholic fatty liver disease. World J Gastroenterol 2017; 23:3407-3417. [PMID: 28596677 PMCID: PMC5442077 DOI: 10.3748/wjg.v23.i19.3407] [Citation(s) in RCA: 69] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2016] [Revised: 02/28/2017] [Accepted: 04/13/2017] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. Its pathogenesis is complex and not yet fully understood. Over the years many studies have proposed various pathophysiological hypotheses, among which the currently most widely accepted is the "multiple parallel hits" theory. According to this model, lipid accumulation in the hepatocytes and insulin resistance increase the vulnerability of the liver to many factors that act in a coordinated and cooperative manner to promote hepatic injury, inflammation and fibrosis. Among these factors, adipose tissue dysfunction and subsequent chronic low grade inflammation play a crucial role. Recent studies have shown that vitamin D exerts an immune-regulating action on adipose tissue, and the growing wealth of epidemiological data is demonstrating that hypovitaminosis D is associated with both obesity and NAFLD. Furthermore, given the strong association between these conditions, current findings suggest that vitamin D may be involved in the relationship between adipose tissue dysfunction and NAFLD. The purpose of this review is to provide an overview of recent advances in the pathogenesis of NAFLD in relation to adipose tissue dysfunction, and in the pathophysiology linking vitamin D deficiency with NAFLD and adiposity, together with an overview of the evidence available on the clinical utility of vitamin D supplementation in cases of NAFLD.
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Yang BB, Chen YH, Zhang C, Shi CE, Hu KF, Zhou J, Xu DX, Chen X. Low vitamin D status is associated with advanced liver fibrosis in patients with nonalcoholic fatty liver disease. Endocrine 2017; 55:582-590. [PMID: 27796814 DOI: 10.1007/s12020-016-1152-x] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2016] [Accepted: 10/17/2016] [Indexed: 02/06/2023]
Abstract
Several studies explored the association between vitamin D status and nonalcoholic fatty liver disease with contradictory results. We aimed to investigate the association between vitamin D status, inflammatory cytokines and liver fibrosis in nonalcoholic fatty liver disease patients. Two hundred nineteen nonalcoholic fatty liver disease patients and 166 age- and gender- matched healthy controls were recruited for this study. Serum 25(OH)D was measured by radioimmunoassay. Serum interleukin-8 and transforming growth factor-β1 were measured using ELISA. Serum 25(OH)D was only marginally decreased in nonalcoholic fatty liver disease patients. Interestingly, serum 25(OH)D was markedly reduced in nonalcoholic fatty liver disease patients with advanced liver fibrosis compared to nonalcoholic fatty liver disease patients with indeterminate liver fibrosis and no advanced fibrosis. Logistic regression analysis showed that there was an inverse association between serum 25(OH)D and severity of liver fibrosis in nonalcoholic fatty liver disease patients. Further analysis showed that serum interleukin-8 was elevated in nonalcoholic fatty liver disease patients, the highest interleukin-8 in patients with advanced fibrosis. An inverse correlation between serum 25(OH)D and interleukin-8 was observed in nonalcoholic fatty liver disease patients with and without liver fibrosis. Although serum transforming growth factor-β1 was slightly elevated in nonalcoholic fatty liver disease patients, serum transforming growth factor-β1 was reduced in nonalcoholic fatty liver disease patients with advanced fibrosis. Unexpectedly, a positive correlation between serum 25(OH)D and transforming growth factor-β1 was observed in nonalcoholic fatty liver disease patients with advanced fibrosis. In conclusion, low vitamin D status is associated with advanced liver fibrosis in nonalcoholic fatty liver disease patients. Interleukin-8 may be an important mediator for hepatic fibrosis in nonalcoholic fatty liver disease patients with low vitamin D status.
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Affiliation(s)
- Bing-Bing Yang
- Department of Gastroenterology, Fourth Affiliated Hospital of Anhui Medical University, Hefei, 230032, China
| | - Yuan-Hua Chen
- Department of Toxicology, Anhui Medical University, Hefei, 230032, China
- Department of Histology and Embryology, Anhui Medical University, Hefei, 230032, China
| | - Cheng Zhang
- Department of Toxicology, Anhui Medical University, Hefei, 230032, China
| | - Chang-E Shi
- Department of Gastroenterology, Fourth Affiliated Hospital of Anhui Medical University, Hefei, 230032, China
| | - Kai-Feng Hu
- Department of Gastroenterology, Fourth Affiliated Hospital of Anhui Medical University, Hefei, 230032, China
| | - Ju Zhou
- Department of Gastroenterology, Fourth Affiliated Hospital of Anhui Medical University, Hefei, 230032, China
| | - De-Xiang Xu
- Department of Toxicology, Anhui Medical University, Hefei, 230032, China.
| | - Xi Chen
- Department of Gastroenterology, First Affiliated Hospital of Anhui Medical University, Hefei, 230032, China.
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