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Wang S, Sun W, Cheng Y, Wang L, Ma S, Jing F, Zhang X, Zhou X. Relationship between plasma 12,13-diHOME level and nonalcoholic fatty liver disease in patients with type 2 diabetes and obesity. Minerva Endocrinol (Torino) 2025; 50:72-83. [PMID: 33855386 DOI: 10.23736/s2724-6507.21.03424-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
BACKGROUND 12,13-dihydroxy-9Z-octadecenoic acid (12,13-diHOME) was one of the newly found lipokines. The goal of this study was to investigate whether the 12,13-diHOME was associated with related metabolic markers of nonalcoholic fatty liver disease (NAFLD) in a Chinese population with type 2 diabetes (T2DM) and obesity. METHODS This cross-sectional study enrolled 202 subjects with T2DM. Anthropometric parameters, 12,13-diHOME, serum lipids levels, fasting blood-glucose (FBG), serum glycosylated hemoglobin (HbA1c), fasting insulin (FINS), homeostasis model assessment of insulin resistance (HOMA-IR), liver and kidney function parameters were collected. NAFLD was diagnosed based on abdominal ultrasonography examination results. A computer-aided ultrasound quantitative method was applied to evaluate the liver fat content (LFC). RESULTS The number of the patients with fatty liver was 139 (68.81%) and those with non-fatty liver was 63 (31.19%). Subjects with NAFLD had a higher body mass index (BMI), diastolic blood pressure, serum alanine aminotransferase (ALT), triglyceride (TG), HOMA-IR, LFC, P<0.05 for all. But no significant difference was found in plasma 12,13-diHOME level (P=0.967), though its level trend was higher in non-NAFLD group. Plasma 12,13-diHOME was positively correlated with aspartate aminotransferase (AST), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), blood urea nitrogen (BUN), free fatty acid (FFA), C-peptide, FINS and HOMA-IR. It was negatively correlated with height, body weight, glomerular filtration rate (eGFR) and HbA1c. CONCLUSIONS Although 12,13-diHOME was correlated with AST, TC, HDL-C, BUN, FFA, C-peptide, FINS, HOMA-IR, eGFR and HbA1c, there was no significant difference in 12,13-diHOME level between the two groups. However, more research should be carried on about this newly-found lipokine.
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Affiliation(s)
- Sichao Wang
- Department of Endocrinology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
- Department of Infectious Diseases and Hepatology, The Second Hospital of Shandong University, Jinan, China
| | - Weixia Sun
- Department of Endocrinology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Yiping Cheng
- Department of Endocrinology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Lei Wang
- Department of Endocrinology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Shizhan Ma
- Department of Endocrinology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Fei Jing
- Department of Endocrinology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Xiujuan Zhang
- Department of Endocrinology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Xinli Zhou
- Department of Endocrinology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China -
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Kumar M, Parchani A, Kant R, Das A. Relationship Between Vitamin D Deficiency and Non-alcoholic Fatty Liver Disease: A Cross-Sectional Study From a Tertiary Care Center in Northern India. Cureus 2023; 15:e34921. [PMID: 36938188 PMCID: PMC10015758 DOI: 10.7759/cureus.34921] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/13/2023] [Indexed: 02/16/2023] Open
Abstract
Background Vitamin D levels are strongly associated with myocardial infarction, coronary artery disease, heart dysfunction, and even mortality. Non-alcoholic fatty liver disease (NAFLD) is a prevalent hepatic illness whose incidence has grown dramatically over the past several decades. Methodology This observational, cross-sectional study was conducted over 1.5 years (January 2019 to June 2020) at the Department of General Medicine of a tertiary care hospital in northern India on 100 adult patients with NAFLD admitted to the emergency ward, intensive care unit, and medical ward. Results In our study, of the 100 patients, 45.0%, 16.0%, and 39.0% of patients exhibited vitamin D deficiency, insufficiency, and sufficiency, respectively. Vitamin D deficiency was the highest among those aged 41-50 (54.2%) and lowest among those aged 30-40 (29.0%). We observed that vitamin D deficiency was less prevalent in people with a normal body mass index (39.1%) than in those who were overweight (91.7%). There was a significant (p < 0.05) association between the severity of vitamin D deficiency and the presence of hepatomegaly, splenomegaly, and ascites. Overall, the incidence of fatty liver was 49% among patients. There was a significant (p = 0.0001) correlation between fatty liver and serum vitamin D levels. The association between the proportion of patients with fatty liver and the degree of vitamin D deficiency was found to be significant (p = 0.04). The relationship between the distribution of patients according to insulin resistance and the degree of vitamin D deficiency was also statistically significant (p < 0.001). Conclusions Vitamin D deficiency is associated with an increased risk of NAFLD, as well as with the severity of NAFLD.
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Affiliation(s)
- Manoj Kumar
- Department of General Medicine, Uttar Pradesh University of Medical Sciences, Saifai, IND
| | - Ashwin Parchani
- Department of General Medicine, All India Institute of Medical Sciences, Rishikesh, Rishikesh, IND
| | - Ravi Kant
- Department of General Medicine, All India Institute of Medical Sciences, Rishikesh, Rishikesh, IND
| | - Arindam Das
- Department of General Medicine, Uttar Pradesh University of Medical Sciences, Saifai, IND
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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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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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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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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: 10] [Impact Index Per Article: 1.7] [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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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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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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Rafiq R, Walschot F, Lips P, Lamb HJ, de Roos A, Rosendaal FR, Heijer MD, de Jongh RT, de Mutsert R. Associations of different body fat deposits with serum 25-hydroxyvitamin D concentrations. Clin Nutr 2018; 38:2851-2857. [PMID: 30635144 DOI: 10.1016/j.clnu.2018.12.018] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2018] [Revised: 12/11/2018] [Accepted: 12/13/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Obesity is a well-established risk factor of vitamin D deficiency. However, it is unclear which fat deposit is most strongly related to serum 25-hydroxyvitamin D (25(OH)D) concentrations. Our aim was to distinguish the specific contributions of total body fat (TBF), abdominal subcutaneous adipose tissue (aSAT), visceral adipose tissue (VAT) and hepatic fat on 25(OH)D concentrations. METHODS We performed a cross-sectional analysis of the Netherlands Epidemiology of Obesity study, a population-based cohort study. We used linear regression analyses to examine associations of TBF, aSAT, VAT (n = 2441) and hepatic fat (n = 1980) with 25(OH)D concentrations. Standardized values were used to compare the different fat deposits. RESULTS Mean (SD) age and 25(OH)D concentrations of the study population was 56 (6) years and 70.8 (24.2) nmol/L, respectively. TBF was inversely associated with 25(OH)D concentrations in women, but not in men. One percent higher TBF was associated with 0.40 nmol/L (95%CI: -0.67 to -0.13) lower 25(OH)D. aSAT was not associated with 25(OH)D concentrations. One cm2 higher VAT was associated with 0.05 nmol/L (-0.09 to -0.02) lower 25(OH)D in men, and 0.06 nmol/L (-0.10 to -0.01) lower 25(OH)D in women. Hepatic fat was only associated with 25(OH)D in men. A tenfold increase in hepatic fat was associated with 6.21 nmol/L (-10.70 to -1.73) lower 25(OH)D. Regressions with standardized values showed VAT was most strongly related to 25(OH)D. CONCLUSIONS In women, TBF and VAT were inversely related to 25(OH)D concentrations. In men, VAT and hepatic fat were inversely related to 25(OH)D concentrations. In both groups, VAT was most strongly associated with 25(OH)D concentrations.
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Affiliation(s)
- Rachida Rafiq
- Department of Internal Medicine and Endocrinology, VU University Medical Center, Amsterdam Movement Sciences, Amsterdam, the Netherlands.
| | - Floor Walschot
- Department of Internal Medicine and Endocrinology, VU University Medical Center, Amsterdam Movement Sciences, Amsterdam, the Netherlands
| | - Paul Lips
- Department of Internal Medicine and Endocrinology, VU University Medical Center, Amsterdam Movement Sciences, Amsterdam, the Netherlands
| | - Hildo J Lamb
- Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands
| | - Albert de Roos
- Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands
| | - Frits R Rosendaal
- Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands
| | - Martin den Heijer
- Department of Internal Medicine and Endocrinology, VU University Medical Center, Amsterdam Movement Sciences, Amsterdam, the Netherlands; Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands
| | - Renate T de Jongh
- Department of Internal Medicine and Endocrinology, VU University Medical Center, Amsterdam Movement Sciences, Amsterdam, the Netherlands
| | - Renée de Mutsert
- Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands
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11
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Sun X, Cao ZB, Tanisawa K, Oshima S, Higuchi M. Serum 25-Hydroxyvitamin D Concentrations Are Inversely Correlated with Hepatic Lipid Content in Male Collegiate Football Athletes. Nutrients 2018; 10:nu10070942. [PMID: 30037116 PMCID: PMC6073760 DOI: 10.3390/nu10070942] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2018] [Revised: 07/19/2018] [Accepted: 07/20/2018] [Indexed: 12/19/2022] Open
Abstract
Lower serum 25-hydroxyvitamin D (25(OH)D) concentrations are associated with more weight and fat mass gain in adults in the general population, but it is unknown whether this is the case in collegiate football athletes with greater body weight. This study aimed to investigate associations of serum 25(OH)D concentrations with body fat and ectopic fat accumulation, and to determine which fat indicators are closely related to serum 25(OH)D in male collegiate football athletes. Thirty-four collegiate athletes aged 21 years were recruited. Serum 25(OH)D concentrations and the levels of visceral fat area (VFA), vastus lateralis intramyocellular lipid (IMCL), extramyocellular lipid (EMCL), and intrahepatic lipid (IHCL) were measured. Serum 25(OH)D concentrations were negatively associated with the IHCL values (r = −0.372, p = 0.030), and the relationship remained after adjustment for several factors (r = −0.378, p = 0.047). Additionally, multiple stepwise regression analysis of IHCL content as the dependent variable indicated that 25(OH)D concentrations were a stronger predictor of IHCL content (β = −0.363, p = 0.030) than % body fat and VO2peakFFM. Higher serum 25(OH)D concentrations are more closely related to lower IHCL content rather than any other fat indicators, suggesting that increasing serum 25(OH)D concentrations may have some effect that inhibits lipid accumulation in hepatic tissue, especially in heavy athletes.
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Affiliation(s)
- Xiaomin Sun
- School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China.
- Global Health Institute, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China.
- Faculty of Sport Sciences, Waseda University, Tokorozawa, Saitama 359-1192, Japan.
| | - Zhen-Bo Cao
- School of Kinesiology, Shanghai University of Sport, 399 Chang Hai Road, Shanghai 200438, China.
| | - Kumpei Tanisawa
- Faculty of Sport Sciences, Waseda University, Tokorozawa, Saitama 359-1192, Japan.
- Department of Physical Activity Research, National Institutes of Biomedical Innovation, Health and Nutrition, Tokyo 162-8636, Japan.
| | - Satomi Oshima
- Faculty of Sport Sciences, Waseda University, Tokorozawa, Saitama 359-1192, Japan.
| | - Mitsuru Higuchi
- Faculty of Sport Sciences, Waseda University, Tokorozawa, Saitama 359-1192, Japan.
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12
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Abstract
In the past few years, a growing body of clinical evidence has highlighted the risk of vitamin D deficiency in patients with chronic hepatitis C and that vitamin D levels are associated with the course of hepatitis C virus (HCV) infection, adverse effects, and treatment response to peginterferon/ribavirin. Recently, studies have found that vitamin D status is related to drug resistance and increased risk of infection in patients with liver cirrhosis. Vitamin D-related gene polymorphisms have been found to explain the interactions between vitamin D deficiency and HCV infection, offering a new perspective toward understanding the current problems such as the development of insulin resistance and racial differences in sustained virological response. Studies have been conducted to determine whether vitamin D supplementation as an adjuvant yields a better result compared with traditional HCV treatment. Here, we provide a brief review of the past and present knowledge of vitamin D in HCV infection.
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13
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Zhu X, Yan H, Xia M, Chang X, Xu X, Wang L, Sun X, Lu Y, Bian H, Li X, Gao X. Metformin attenuates triglyceride accumulation in HepG2 cells through decreasing stearyl-coenzyme A desaturase 1 expression. Lipids Health Dis 2018; 17:114. [PMID: 29759071 PMCID: PMC5952420 DOI: 10.1186/s12944-018-0762-0] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2018] [Accepted: 04/26/2018] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The prevalence of nonalcoholic fatty liver disease (NAFLD) has increased worldwide. Metformin decreases triglyceride (TG) accumulation in hepatocytes in vivo and in vitro. Stearyl-coenzyme A desaturase 1 (SCD1) knockout mice also show decreased liver TG accumulation; however, whether SCD1 plays a role in the effect of metformin on TG accumulation is unknown. Therefore, the aim of this study was to investigate whether SCD1 mediated the effect of metformin on TG accumulation. METHODS HepG2 and AML12 cells were exposed to high glucose and high insulin with or without metformin. An adenovirus was used for the SCD1 knockdown and overexpression. The triglyceride level in cells was detected. The expression of related genes was detected by Western blot and quantitative real-time PCR. A dual-luciferase reporter assay was used to determine the effect of metformin on the transcriptional activity of the SCD1 promoter. RESULTS Metformin decreased TG accumulation to normal level in HepG2 cells exposed to high glucose and high insulin. The expression of SCD1 and fatty acid synthetase (FAS) was also decreased to normal level by metformin. Knockdown of SCD1 mimicked the effect of metformin on decreasing TG levels in AML12 cells, and the overexpression of SCD1 attenuated the effect of metformin on decreasing TG accumulation in HepG2 cells. The dual-luciferase reporter assay showed that the transcriptional activity of the SCD1 promoter (- 550/+ 199) after metformin treatment was 2-fold lower compared to control group in HepG2 cells. Additionally, the phosphorylation of AMPK after metformin treatment was 2-fold higher, and the expression of sterol regulatory element-binding protein-1c (SREBP-1c) after metformin treatment was about 2-fold lower compared to high glucose and high insulin group in HepG2 cells. CONCLUSIONS Together, these results reveal that metformin reduces TG accumulation in HepG2 cells via inhibiting the expression of SCD1.
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Affiliation(s)
- Xiaopeng Zhu
- Department of Endocrinology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
- Institute for Metabolic Disease, Fudan University, Shanghai, 200032, China
| | - Hongmei Yan
- Department of Endocrinology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
- Institute for Metabolic Disease, Fudan University, Shanghai, 200032, China
| | - Mingfeng Xia
- Department of Endocrinology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
- Institute for Metabolic Disease, Fudan University, Shanghai, 200032, China
| | - Xinxia Chang
- Department of Endocrinology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
- Institute for Metabolic Disease, Fudan University, Shanghai, 200032, China
| | - Xi Xu
- Department of Endocrinology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
- Institute for Metabolic Disease, Fudan University, Shanghai, 200032, China
| | - Liu Wang
- Department of Endocrinology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
- Institute for Metabolic Disease, Fudan University, Shanghai, 200032, China
| | - Xiaoyang Sun
- Department of Endocrinology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
- Institute for Metabolic Disease, Fudan University, Shanghai, 200032, China
| | - Yan Lu
- Department of Endocrinology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
- Institute for Metabolic Disease, Fudan University, Shanghai, 200032, China
| | - Hua Bian
- Department of Endocrinology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
- Institute for Metabolic Disease, Fudan University, Shanghai, 200032, China.
| | - Xiaoying Li
- Department of Endocrinology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
- Institute for Metabolic Disease, Fudan University, Shanghai, 200032, China
| | - Xin Gao
- Department of Endocrinology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
- Institute for Metabolic Disease, Fudan University, Shanghai, 200032, China
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14
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Sun X, Cao ZB, Tanisawa K, Taniguchi H, Kubo T, Higuchi M. Effects of chronic endurance exercise training on serum 25(OH)D concentrations in elderly Japanese men. Endocrine 2018; 59:330-337. [PMID: 29170904 DOI: 10.1007/s12020-017-1478-z] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2017] [Accepted: 11/16/2017] [Indexed: 01/02/2023]
Abstract
BACKGROUND Higher levels of physical activity and cardiorespiratory fitness are positively related to serum 25-hydroxyvitamin D [25(OH)D] concentrations; however, the response of 25(OH)D concentrations to chronic endurance exercise training is unclear. Therefore, the purpose of this study was to elucidate whether serum 25(OH)D concentrations were directly increased by 5 weeks of endurance exercise training and influenced by changes in body fat in elderly men. METHODS Twenty elderly Japanese men were randomized to either the 5-week endurance exercise training group (ET group; N = 10) or the sedentary control group (SC group; N = 10). Fasting blood samples were collected to determine serum 25(OH)D and other blood parameters. The visceral fat area and hepatic fat content were assessed by magnetic resonance imaging and proton magnetic resonance spectroscopy, respectively. RESULTS After 5 weeks of endurance exercise training, the levels of maximal oxygen uptake (VO2 max) were significantly increased from 23.3 at baseline to 28.1 mL/kg/min at the endpoint for the ET group; levels were unchanged for the SC group. A significant seasonal reduction in serum 25(OH)D concentrations was observed in the SC group (P < 0.05), while no change was found in the ET group. The results may be partly attributed to the slight decrease in intrahepatic fat in the ET group. No changes were observed in percent body fat or visceral fat area. CONCLUSIONS The results of our study suggest that 5 weeks of endurance training could inhibit the seasonal reduction in serum 25(OH)D concentrations without changes in body fat.
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Affiliation(s)
- Xiaomin Sun
- School of Public Health, Xi' an Jiaotong University Health Science Center, 710061, Xi'an, China
- Global Health Institute, Xi'an Jiaotong University Health Science Center, 710061, Xi'an, China
- Faculty of Sport Sciences, Waseda University, Tokorozawa, Saitama, 359-1192, Japan
| | - Zhen-Bo Cao
- School of Kinesiology, Shanghai University of Sport, 399 Chang Hai Road, 200438, Shanghai, China.
- Faculty of Sport Sciences, Waseda University, Tokorozawa, Saitama, 359-1192, Japan.
| | - Kumpei Tanisawa
- Department of Physical Activity Research, National Institutes of Biomedical Innovation, Health and Nutrition, Tokyo, 162-8636, Japan
- Faculty of Sport Sciences, Waseda University, Tokorozawa, Saitama, 359-1192, Japan
| | | | - Takafumi Kubo
- Graduate School of Sport Sciences, Waseda University, Tokorozawa, Saitama, 359-1192, Japan
| | - Mitsuru Higuchi
- Faculty of Sport Sciences, Waseda University, Tokorozawa, Saitama, 359-1192, Japan
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15
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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: 39] [Impact Index Per Article: 5.6] [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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Tabrizi R, Moosazadeh M, Lankarani KB, Akbari M, Heydari ST, Kolahdooz F, Samimi M, Asemi Z. The effects of vitamin D supplementation on metabolic profiles and liver function in patients with non-alcoholic fatty liver disease: A systematic review and meta-analysis of randomized controlled trials. Diabetes Metab Syndr 2017; 11 Suppl 2:S975-S982. [PMID: 28751149 DOI: 10.1016/j.dsx.2017.07.025] [Citation(s) in RCA: 42] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2017] [Accepted: 07/16/2017] [Indexed: 02/05/2023]
Abstract
BACKGROUND A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to summarize the evidence on the effect of vitamin D supplementation on metabolic profiles in patients with non-alcoholic fatty liver disease (NAFLD). METHODS We systematically searched PubMed, EMBASE and five other databases to identify all RCTs investigating the association between vitamin D and NAFLD up until 5 October 2016. Seven RCTs with 452 participants (227 patients and 225 controls) were included in the meta-analysis. RESULTS The results showed that vitamin D administration had no beneficial effect on fasting plasma glucose (FPG) (standardized mean difference [SMD]-0.23; 95% confidence interval [CI], -0.88, 0.42), insulin (SMD -1.09; 95% CI, -2.70,0.52) and homeostasis model assessment of insulin resistance (HOMA-IR) (SMD -1.89; 95% CI, -3.88,0.09). Vitamin D supplementation also had no effect on lipid profiles including triglycerides (SMD -0.36; 95% CI, -1.77, 1.04), and total-cholesterol (SMD -0.46; 95% CI: -1.3, 0.39), as well as on aspartate transaminase (AST) (SMD -0.53; 95% CI, -1.11, 0.05), alanine aminotransferase (ALT) (SMD -0.66; 95% CI, -1.43,0.11), and body mass index (BMI) (SMD -0.25; 95% CI, -0.76,0.27). CONCLUSIONS Vitamin D supplementation had no effect on FPG, insulin, HOMA-IR, triglycerides, total-, LDL-cholesterol, AST, ALT, and BMI.
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Affiliation(s)
- Reza Tabrizi
- Health Policy Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mahmood Moosazadeh
- Health Sciences Research Center, Faculty of Health, Mazandaran University of Medical Sciences, Sari, Iran
| | - Kamran B Lankarani
- Health Policy Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Maryam Akbari
- Health Policy Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Seyed Taghi Heydari
- Health Policy Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Fariba Kolahdooz
- Indigenous and Global Health Research, Department of Medicine, University of Alberta, Edmonton, Canada
| | - Mansooreh Samimi
- Department of Gynecology and Obstetrics, School of Medicine, Kashan University of Medical Sciences, Kashan, Iran
| | - Zatollah Asemi
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran.
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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: 9] [Impact Index Per Article: 1.1] [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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Vitamin D Status of Residents in Taiyuan, China and Influencing Factors. Nutrients 2017; 9:nu9080898. [PMID: 28820448 PMCID: PMC5579691 DOI: 10.3390/nu9080898] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2017] [Revised: 08/17/2017] [Accepted: 08/17/2017] [Indexed: 02/07/2023] Open
Abstract
High prevalence of vitamin D deficiency has been reported worldwide. Residents of Taiyuan, China, were predicted to be at high risk of vitamin D deficiency due to its high latitude, heavy air pollution, and cultural sun avoidance. This study investigated the vitamin D status of office workers, and explored the potential determinants of capillary 25-hydroxyvitamin D (25(OH)D) concentration as well as the relationship between 25(OH)D and metabolic syndrome. Two hundred participants, aged 20 to 80 years, were recruited. Capillary dried blood spot (DBS) 25(OH)D was measured; together with anthropometric (height, weight, and waist circumference), biochemical (serum lipid profile and fasting glucose) measures and a lifestyle questionnaire. Thirty-four percent of participants had 25(OH)D concentrations below 30 nmol/L, indicating deficient vitamin D status. Women’s 25(OH)D (median; 32.7 nmol/L (upper and lower quartile; 25.8, 43.8)) was significantly lower than men (44.0 nmol/L (32.3, 55.4)) (p < 0.01). Female gender, higher fasting glucose, and increased smoking (p < 0.05) were negatively associated with 25(OH)D concentration. However, there was no association found between metabolic syndrome (MetS) and 25(OH)D concentration and no significant difference in vitamin D status between men or women with MetS compared to healthy individuals. Vitamin D deficiency was common in urban residents of Taiyuan in winter and more so in women than men.
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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: 57] [Impact Index Per Article: 7.1] [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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Paquissi FC. Immune Imbalances in Non-Alcoholic Fatty Liver Disease: From General Biomarkers and Neutrophils to Interleukin-17 Axis Activation and New Therapeutic Targets. Front Immunol 2016; 7:490. [PMID: 27891128 PMCID: PMC5104753 DOI: 10.3389/fimmu.2016.00490] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2016] [Accepted: 10/25/2016] [Indexed: 12/21/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is an increasing problem worldwide and is associated with negative outcomes such as cirrhosis, hepatocellular carcinoma, insulin resistance, diabetes, and cardiovascular events. Current evidence shows that the immune response has an important participation driving the initiation, maintenance, and progression of the disease. So, various immune imbalances, from cellular to cytokines levels, have been studied, either for better compression of the disease pathophysiology or as biomarkers for severity assessment and outcome prediction. In this article, we performed a thorough review of studies that evaluated the role of inflammatory/immune imbalances in the NAFLD. At the cellular level, we gave special focus on the imbalance between neutrophils and lymphocytes counts (the neutrophil-to-lymphocyte ratio), and that which occurs between T helper 17 (Th17) and regulatory T cells as emerging biomarkers. By extension, we reviewed the reflection of these imbalances at the molecular level through pro-inflammatory cytokines including those involved in Th17 differentiation (IL-6, IL-21, IL-23, and transforming growth factor-beta), and those released by Th17 cells (IL-17A, IL-17F, IL-21, and IL-22). We gave particular attention to the role of IL-17, either produced by Th17 cells or neutrophils, in fibrogenesis and steatohepatitis. Finally, we reviewed the potential of these pathways as new therapeutic targets in NAFLD.
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