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Lin CM, Hsieh CH, Lee CH, Pei D, Lin JD, Wu CZ, Liang YJ, Hung YJ, Chen YL. Predictive Value of Serum Gamma-glutamyltranspeptidase for Future Cardiometabolic Dysregulation in Adolescents- a 10-year longitudinal study. Sci Rep 2017; 7:9636. [PMID: 28851958 PMCID: PMC5574888 DOI: 10.1038/s41598-017-09719-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2016] [Accepted: 06/27/2017] [Indexed: 12/29/2022] Open
Abstract
Serum gamma-glutamyltransferase (γ-GT) is implicated in the pathogenesis of atherosclerosis and metabolic syndrome (MetS) in adults. The relationships between γ-GT and cardiometabolic dysregulation remains unclear in adolescents. We enrolled 7,072 Taiwanese adolescents and followed them for a median of 6.8 years. The optimal cut-off values (CoVs) of baseline γ-GT to predict future MetS, hypertension (HTN), and type 2 diabetes (T2DM) were determined by receiving operating characteristic (ROC) curve. Using these CoVs, the participants were divided into normal- and high-level groups. Cox proportional hazard analysis was used to calculate hazard ratios (HRs) for the subjects with a high level of γ-GT for the risk of future cardiometabolic dysregulation. Serum γ-GT was significantly higher in the subjects with MetS than in those without MetS at baseline (p < 0.001). The optimal CoVs of γ-GT were 12 U/L for boys and 11 U/L for girls. In multivariate Cox regression analysis, a higher serum γ-GT level increased the risk of future MetS (HRs 1.98 and 2.85 for boys and girls, respectively, both p < 0.001), but not new onset HTN and T2DM. In conclusion, serum γ-GT levels not only demonstrated an excellent correlation with the presence of MetS and also in predicting future MetS in adolescents.
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Affiliation(s)
- Chien-Ming Lin
- Department of Pediatrics, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.,Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan
| | - Chang-Hsun Hsieh
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Chien-Hsing Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Dee Pei
- Department of Internal Medicine, Cardinal Tien Hospital, School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan
| | - Jiunn-Diann Lin
- Division of Endocrinology, Department of Internal Medicine, Shuang-Ho Hospital, Taipei Medical University, New Taipei City, Taiwan, Republic of China.,Division of Endocrinology and Metabolism, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, Republic of China
| | - Chung-Ze Wu
- Division of Endocrinology, Department of Internal Medicine, Shuang-Ho Hospital, Taipei Medical University, New Taipei City, Taiwan, Republic of China.,Division of Endocrinology and Metabolism, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, Republic of China
| | - Yao-Jen Liang
- Department of Life Science, Graduate Institute of Applied Science and Engineering, College of Science and Engineering, Fu-Jen Catholic University, New Taipei City, Taiwan
| | - Yi-Jen Hung
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
| | - Yen-Lin Chen
- Department of Pathology, Cardinal Tien Hospital, School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan.
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Hwang SH, Kim JH, Wang Z, Lee JY, Lim SS. Analytical Method for the Validation of Three Polyphenols as a Marker Compound for the Standardization of Solidago virgaurea subsp. gigantea Extracts and Antiadipogenesis of Harvesting Time and Location. JOURNAL OF ANALYTICAL METHODS IN CHEMISTRY 2017; 2017:3047408. [PMID: 28819580 PMCID: PMC5551537 DOI: 10.1155/2017/3047408] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 04/21/2017] [Accepted: 06/08/2017] [Indexed: 06/07/2023]
Abstract
Protocatechuic acid (PC), chlorogenic acid (CA), and kaempferol-3-O-rutinoside (K-O-R), isolated from the Solidago virgaurea subsp. gigantea (SV) extract, were quickly and efficiently separated using HPLC. Our chromatographic method was found to effectively separate PC, CA, and K-O-R at retention times of 5.36, 8.22, and 17.04 min, respectively. Linearity of PC, CA, and K-O-R was found to be in the range of 4.85-485.00, 47.5-1900.00, and 8.50-850.00 μg/ml. Recoveries ranged between 101.32 and 103.30%, 95.82 and 100.25%, and 96.18 and 99.37%, for PC, CA, and K-O-R, respectively. The antiadipogenesis activity of SV extracts collected from five different months and from seven different regions was evaluated using an Oil Red O staining assay in 3T3-L1 cells. Extract from SV collected in April from the Ulleung Island produced over 106.89% inhibition of adipogenesis without cytotoxicity at 50 μg/ml. This extract had a high amount of PC and K-O-R. The developed HPLC method was found to be fast, accurate, precise, and reproducible and could be applied to qualitative and quantitative analysis of three bioactive compounds in SV extracts. The SV extract collected in April from Ulleung Island can be used as a functional food ingredient preventing obesity.
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Affiliation(s)
- Seung Hwan Hwang
- Department of Food Science and Nutrition, Hallym University, 1 Hallymdeahak-gil, Chuncheon 24252, Republic of Korea
| | - Ju Hee Kim
- Institute of Natural Medicine, Hallym University, 1 Hallymdeahak-gil, Chuncheon 24252, Republic of Korea
| | - Zhiqiang Wang
- Department of Food Science and Nutrition, Hallym University, 1 Hallymdeahak-gil, Chuncheon 24252, Republic of Korea
| | - Jae-Yong Lee
- Institute of Natural Medicine, Hallym University, 1 Hallymdeahak-gil, Chuncheon 24252, Republic of Korea
- Department of Biochemistry, School of Medicine, Hallym University, 1 Hallymdeahak-gil, Chuncheon 24252, Republic of Korea
| | - Soon Sung Lim
- Department of Food Science and Nutrition, Hallym University, 1 Hallymdeahak-gil, Chuncheon 24252, Republic of Korea
- Department of Biochemistry, School of Medicine, Hallym University, 1 Hallymdeahak-gil, Chuncheon 24252, Republic of Korea
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Wang Z, Hwang SH, Kim JH, Lim SS. Anti-Obesity Effect of the Above-Ground Part of Valeriana dageletiana Nakai ex F. Maek Extract in High-Fat Diet-Induced Obese C57BL/6N Mice. Nutrients 2017; 9:nu9070689. [PMID: 28671595 PMCID: PMC5537804 DOI: 10.3390/nu9070689] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2017] [Revised: 06/16/2017] [Accepted: 06/18/2017] [Indexed: 12/15/2022] Open
Abstract
Valeriana dageletiana Nakai ex F. Maek (VD) has been used as traditional medicine for the treatment of restlessness and sleeping disorders. However, it is still unclear whether obesity in mice can be altered by diet supplementation with VD. In this study, we first investigated the influences of VD on the accumulation of lipid content in 3T3-L1 cells; and the results showed that the above-ground VD extracts (VDAE) suppressed the differentiation of 3T3-L1 preadipocytes in a concentration-dependent manner without cytotoxicity. Thus, the effects of VDAE on preventing obesity were then studied in the C57BL/6N mice for 10 weeks (n = 6): normal-fat diet, high-fat diet (HFD), HFD supplemented with 1% (10 g/kg) Garcinia combogia extract (positive control), and HFD supplemented with 1% (10 g/kg) VDAE. The results showed that VDAE reduced food efficiency ratio, body weight, epididymal adipose and hepatic tissue weight, hepatic lipid metabolites, and triacylglycerol and cholesterol serum levels compared to the high-fat diet group. Moreover, VD significantly inhibited the expression of adipogenic genes, such as PPAR-γ, C/EBP-α, and aP2, and lipogenic genes, such as SREBP-1c, FAS, SCD-1, and CD36, in epididymal adipose tissue and hepatic tissue. These findings indicate anti-adipogenic and anti-lipogenic effects of VDAE and suggest that it could be a potent functional food ingredient for the prevention of high-fat diet-induced obesity.
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Affiliation(s)
- Zhiqiang Wang
- Department of Preventive Medicine and Health Management, Hebei University, Baoding 071002, China.
- Department of Food Science and Nutrition, Hallym University, Chuncheon 24252, Korea.
| | - Seung Hwan Hwang
- Department of Food Science and Nutrition, Hallym University, Chuncheon 24252, Korea.
| | - Ju Hee Kim
- Institute of Natural Medicine, Hallym University, Chuncheon 24252, Korea.
| | - Soon Sung Lim
- Department of Food Science and Nutrition, Hallym University, Chuncheon 24252, Korea.
- Institute of Natural Medicine, Hallym University, Chuncheon 24252, Korea.
- Institute of Korean Nutrition, Hallym University, Chuncheon 24252, Korea.
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Ateyya H, Nader MA, Attia GM, El-Sherbeeny NA. Influence of alpha-lipoic acid on nicotine-induced lung and liver damage in experimental rats. Can J Physiol Pharmacol 2017; 95:492-500. [PMID: 28177698 DOI: 10.1139/cjpp-2016-0366] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
Nicotine mediates some of the injurious effects caused by consuming tobacco products. This work aimed at investigating the defensive role of alpha-lipoic acid (ALA) with its known antioxidant and antiinflammatory effect in nicotine-induced lung and liver damage. Rats were arranged into 4 groups: control, nicotine, ALA, and ALA-nicotine groups. Oxidative stress and antioxidant status were determined by assessing thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD), and glutathione (GSH) levels in lung and liver. Liver enzymes and lipid profiles were measured and pulmonary and hepatic damage were assessed by histopathological examination. Also, serum levels of transforming growth factor beta 1 (TGF-β1) and vascular cell adhesion molecule 1 (VCAM-1) were determined. The results revealed an increase in TBARS in tissues and a reduction in both SOD and GSH activity in the nicotine-treated rats. Nicotine induced high levels of liver enzymes, TGF-β1, VCAM-1, and dyslipidemia with histopathological changes in the lung and liver. ALA administration along with nicotine attenuated oxidative stress and normalized the SOD and GSH levels, ameliorated dyslipidemia, and improved TGF-β1 and VCAM-1 with better histopathology of the lung and liver. The study data revealed that ALA may be beneficial in alleviating nicotine-induced oxidative stress, dyslipidemia, and both lung and liver damage.
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Affiliation(s)
- Hayam Ateyya
- a College of Pharmacy, Taibah University, Al-Madinah Al-Munawarah, Saudi Arabia
- b Department of Clinical Pharmacology, Faculty of Medicine, Cairo University, Egypt
| | - Manar A Nader
- a College of Pharmacy, Taibah University, Al-Madinah Al-Munawarah, Saudi Arabia
- c Faculty of Pharmacy, Mansoura University, Egypt
| | - Ghalia M Attia
- d Department of Anatomy, Faculty of Medicine, Taibah University, Al-Madinah Al-Munawarah, Saudi Arabia
- e Department of Histology and Cell Biology, Faculty of Medicine, Mansoura University, Al Mansoura, Egypt
| | - Nagla A El-Sherbeeny
- f Department of Pharmacology and Toxicology, College of Pharmacy, Taibah University, Al-Madinah Al-Munawarah, Saudi Arabia
- g Department of Clinical Pharmacology, Faculty of Medicine, Suez Canal University, Egypt
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Nazmy EA, El-Khouly OA, Atef H, Said E. Sulforaphane protects against sodium valproate–induced acute liver injury. Can J Physiol Pharmacol 2017; 95:420-426. [DOI: 10.1139/cjpp-2016-0447] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Drug-induced hepatotoxicity is one of the most commonly encountered obstacles in the field of medical practice. Sodium valproate (VPA) is among many drugs with reported hepatotoxic effects. Sulforaphane (SFN) is a thiol compound found in wide abundance in cruciferous plants that has numerous reported therapeutic efficacies. The current investigation sheds light on the potential hepatoprotective effect of SFN against VPA-induced liver injury in rats. Twice daily VPA (700 mg/kg, i.p.) for 7 days induced significant biochemical alterations and hepatic histopathological damage. SFN (0.5 mg/kg, orally) for 7 days significantly boosted liver function biomarkers; it reduced serum alanine transaminase, aspartate aminotransferase, and alkaline phosphatase, and restored serum albumin concentration in a significant manner. Meanwhile, SFN significantly mitigated VPA-induced histopathological alterations. To highlight the mechanisms implicated in the observed hepatoprotective action, hepatic malondialdehyde and tumour necrosis factor α content significantly declined with concomitant increase in hepatic heme oxygenase-1 content and glutathione concentration with SFN treatment. In conclusion, SFN can significantly ameliorate VPA-induced hepatotoxicity and liver injury primarily by direct association between antioxidant and anti-inflammatory properties.
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Affiliation(s)
| | | | - Hoda Atef
- Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Eman Said
- Faculty of Pharmacy, Mansoura University, Mansoura, Egypt
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Wang Z, Kim JH, Jang YS, Kim CH, Lee JY, Lim SS. Anti-obesity effect of Solidago virgaurea var. gigantea extract through regulation of adipogenesis and lipogenesis pathways in high-fat diet-induced obese mice (C57BL/6N). Food Nutr Res 2017; 61:1273479. [PMID: 28326002 PMCID: PMC5345588 DOI: 10.1080/16546628.2016.1273479] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2016] [Revised: 12/08/2016] [Accepted: 12/13/2016] [Indexed: 01/28/2023] Open
Abstract
Background: Obesity is associated with an increase in adipogenesis and is becoming a serious health problem in modern society. Objective: The effects of various Solidago virgaurea var. gigantean (SV) ethanolic aqueous extracts on anti-adipogenesis in 3T3-L1 cells were investigated. In addition, the effect of SV 10% ethanolic extract (SV10E) on preventing obesity was studied in high-fat diet-induced obese mice (C57BL/6 N). Design: The effect of SV10E on preventing obesity was studied in mice (n = 6): normal-fat diet, high-fat diet (HFD), HFD supplemented with 1% (10 g/kg) Garcinia cambogia extract of 60% (–)-hydroxycitric acid (positive control), HFD supplemented with 0.5% (5 g/kg) SV10E, and HFD supplemented with 2% (20 g/kg) SV10E. Results: SV10E showed the highest anti-adipogenic activity in vitro and reduced body weight gain, adipose tissue size, and liver weight, without affecting food intake in vivo. SV10E administration decreased the levels of total triacylglycerol and cholesterol in serum, and lipid metabolites in liver. Adipogenic and lipogenic genes such as PPAR-γ, C/EBP-α, aP2, FAS, SCD-1, SREBP-1c, and CD36 in white adipose tissue and liver were suppressed by SV10E administration. Conclusion: SV10E can be a potent functional food ingredient for preventing HFD-induced obesity by suppressing adipogenesis and lipogenesis.
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Affiliation(s)
- Zhiqiang Wang
- Department of Food Science and Nutrition, Hallym University , Chuncheon , Republic of Korea
| | - Ju Hee Kim
- Institute of Natural Medicine, Hallym University , Chuncheon , Republic of Korea
| | - Young Soo Jang
- Department of Food Science and Nutrition, Hallym University , Chuncheon , Republic of Korea
| | - Chea Ha Kim
- Department of Biochemistry, Institute of Cell Differentiation and Aging, Hallym University , Chuncheon , Republic of Korea
| | - Jae-Yong Lee
- Institute of Natural Medicine, Hallym University, Chuncheon, Republic of Korea; Department of Biochemistry, Institute of Cell Differentiation and Aging, Hallym University, Chuncheon, Republic of Korea
| | - Soon Sung Lim
- Department of Food Science and Nutrition, Hallym University, Chuncheon, Republic of Korea; Institute of Natural Medicine, Hallym University, Chuncheon, Republic of Korea; Institute of Korean Nutrition, Hallym University, Republic of Korea
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Moustafa EM, Thabet NM. Beta-sitosterol upregulated paraoxonase-1 via peroxisome proliferator-activated receptor-γ in irradiated rats. Can J Physiol Pharmacol 2017; 95:661-666. [PMID: 28177669 DOI: 10.1139/cjpp-2016-0397] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
This study was designed to evaluate the effect of beta-sitosterol (BS) on the peroxisome proliferator-activated receptor gamma (PPAR-γ) gene expression role in the activity of paraoxonase (PON-1) enzyme in oxidative stress status of irradiated rats. Animals were exposed to whole body γ-radiation single dose 6 Gy and received BS dose (40 mg·(kg body mass)-1·day -1, orally). In liver tissue, gene expression of PPAR-γ ligand was determined. Oxidative stress marker (malondialdehyde, MDA) and antioxidant enzyme activities (superoxide dismutase (SOD), catalase (CAT), PON-1, and arylesterase (ARE)) were assayed in serum and liver tissue. Also, serum lipid profile (cholesterol, triglycerides (TG), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c)) was measured. In irradiated animals that received BS, expression of PPAR-γ ligand increase significantly associated with increase in PON-1 and ARE enzyme activities. Also, the activities of SOD, CAT enzymes, and HDL-c levels display elevation. By contrast, significant decrease in MDA content, cholesterol, TG, and LDL-c levels were revealed after BS administration. Our findings in this study provide the evidence that BS has radio-protective effect via regulating the gene expression of PPAR-γ, causing an increase in PON-1 and ARE enzyme activities. This action of BS is due to its free radical scavenging properties, antioxidant effect, lowering of cholesterol, and PPAR-γ agonist properties.
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Affiliation(s)
- Enas Mahmoud Moustafa
- Radiation Biology Department, National Centre for Radiation Research and Technology, Atomic Energy Authority, Cairo, Egypt.,Radiation Biology Department, National Centre for Radiation Research and Technology, Atomic Energy Authority, Cairo, Egypt
| | - Noura Magdy Thabet
- Radiation Biology Department, National Centre for Radiation Research and Technology, Atomic Energy Authority, Cairo, Egypt.,Radiation Biology Department, National Centre for Radiation Research and Technology, Atomic Energy Authority, Cairo, Egypt
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Gliozzi M, Maiuolo J, Oppedisano F, Mollace V. The effect of bergamot polyphenolic fraction in patients with non alcoholic liver steato-hepatitis and metabolic syndrome. PHARMANUTRITION 2016. [DOI: 10.1016/j.phanu.2015.11.003] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
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Barengolts E. GUT MICROBIOTA, PREBIOTICS, PROBIOTICS, AND SYNBIOTICS IN MANAGEMENT OF OBESITY AND PREDIABETES: REVIEW OF RANDOMIZED CONTROLLED TRIALS. Endocr Pract 2016; 22:1224-1234. [PMID: 27409822 DOI: 10.4158/ep151157.ra] [Citation(s) in RCA: 94] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
OBJECTIVE To review the data from randomized controlled trials (RCTs) for the roles of microbiota, pre-, pro- and synbiotics in metabolic conditions (obesity, prediabetes, and diabetes mellitus type 2 [DM2]). METHODS Primary literature was reviewed on the topics including RCTs of pre-, pro- and synbiotics use for metabolic disease. RESULTS Gut bacteria (microbiota) benefit digestion and have multiple other functions. Microbiota could increase harvesting of energy from the food and cause subclinical inflammation seen in metabolic disorders. Diet-related interventions including prebiotics, probiotics, and synbiotics (combining pre-and probiotics) may benefit metabolic conditions. Prebiotics are complex carbohydrates (i.e., dietary fiber). Results of RCTs of prebiotics suggested a neutral effect on body weight, decreased fasting and postprandial glucose, and improved insulin sensitivity and lipid profile. Some inflammation markers were reduced, sometimes substantially (20-30%). RCTs for probiotics demonstrated significant but small effects on body weight (<3%) and metabolic parameters. The effect was seen mostly with fermented milk or yogurt compared to capsule form, consumption for at least 8 weeks, and use of multiple rather than a single bacterial strain. Changes in microbiota were seen at times with both pre- and probiotics. Pickled and fermented foods, particularly vegetables and beans, could serve as a dietary source of pre-, pro-, and synbiotics. These foods showed possible benefits for morbidity and mortality in prospective cohort studies. CONCLUSION Pre-, pro-, and synbiotics could prove useful, but further research is needed to clarify their clinical relevance for the prevention and management of metabolic disease. ABBREVIATIONS A1c = glycohemoglobin A1c CI = confidence interval CVD = cardiovascular disease GMB = gut (large bowel) microbiota DM2 = diabetes mellitus type 2 HOMA-IR = homeostatic model assessment of insulin resistance LDL = low-density lipoprotein LPS = lipopolysaccharide NAFLD = nonalcoholic fatty liver disease RCT = randomized controlled trial SMD = standardized mean difference TG = triglycerides.
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Akinyemiju T, Meng Q, Vin-Raviv N. Association between body mass index and in-hospital outcomes: Analysis of the nationwide inpatient database. Medicine (Baltimore) 2016; 95:e4189. [PMID: 27428218 PMCID: PMC4956812 DOI: 10.1097/md.0000000000004189] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
IMPORTANCE Over one-third of American adults (36%) are obese and more than two-thirds (69%) are overweight. The impact of obesity on hospitalization outcomes is not well understood. OBJECTIVE To examine the association between body mass index (BMI) and overall, cancer, chronic obstructive pulmonary disease (COPD), asthma, and cardiovascular disease (CVD)-specific in-hospital mortality; postsurgical complications; and hospital length of stay (LOS). DESIGN Cross-sectional study. SETTING Representative sample of US hospitals included in the Health Cost and Utilization Project Nationwide Inpatient Sample database. PARTICIPANTS We obtained data for patients admitted with a primary diagnosis of cancer, COPD, asthma, and CVD. MAIN OUTCOME In-hospital mortality, postsurgical complications, and hospital LOS. RESULTS A total of 800,417 patients were included in this analysis. A higher proportion of Blacks (26.8%; 12.5%) and Whites (23.3%; 8.7%) had BMI of 40 to 49.9 and ≥50, respectively, compared with Hispanics (20.4%; 7.3%). Compared with normal BMI patients, the odds of in-hospital mortality increased 3.6-fold (odds ratio [OR] 3.62, 95% confidence interval [CI]: 3.37-3.89) for preobese patients, 6.5-fold (OR: 6.52, 95% CI: 5.79-7.34) for patients with BMI: 30 to 31.9, 7.5-fold (OR: 7.57, 95% CI: 6.67-8.59) for patients with BMI: 34 to 35.9, and 1.6- fold (OR: 1.77, 95% CI: 1.56-1.79) for patients with BMI ≥ 50. Compared with normal BMI patients, preobese and overweight patients had shorter hospital stays (β preobese: -1.58, 95% CI: -1.63, -1.52); however, no clear trends were observed for postsurgical complications. CONCLUSIONS The majority of hospitalized patients in this analysis had a BMI > 30, and higher BMI was associated with increased risk of mortality and longer hospital stay.
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Affiliation(s)
- Tomi Akinyemiju
- Department of Epidemiology, University of Alabama at Birmingham
- Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, Alabama
- Correspondence: Tomi Akinyemiju, Department of Epidemiology, University of Alabama at Birmingham, Birmingham, Alabama (e-mail: )
| | - Qingrui Meng
- Department of Epidemiology, University of Alabama at Birmingham
| | - Neomi Vin-Raviv
- University of Northern Colorado Cancer Rehabilitation Institute, Greeley, Colorado
- School of Social Work, College of Health and Human Sciences, Colorado State University, Fort Collins, Colorado, USA
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Razzaghy-Azar M, Nourbakhsh M, Pourmoteabed A, Nourbakhsh M, Ilbeigi D, Khosravi M. An Evaluation of Acylated Ghrelin and Obestatin Levels in Childhood Obesity and Their Association with Insulin Resistance, Metabolic Syndrome, and Oxidative Stress. J Clin Med 2016; 5:61. [PMID: 27348010 PMCID: PMC4961992 DOI: 10.3390/jcm5070061] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2016] [Revised: 05/16/2016] [Accepted: 06/01/2016] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND Ghrelin is a 28-amino acid peptide with an orexigenic property, which is predominantly produced by the stomach. Acylated ghrelin is the active form of this hormone. Obestatin is a 23-amino acid peptide which is produced by post-translational modification of a protein precursor that also produces ghrelin. Obestatin has the opposite effect of ghrelin on food intake. The aim of this study was to evaluate acylated ghrelin and obestatin levels and their ratio in obese and normal-weight children and adolescents, and their association with metabolic syndrome (MetS) parameters. METHODS Serum acyl-ghrelin, obestatin, leptin, insulin, fasting plasma glucose (FPG), lipid profile, and malondialdehyde (MDA) were evaluated in 73 children and adolescents (42 obese and 31 control). Insulin resistance was calculated by a homeostasis model assessment of insulin resistance (HOMA-IR). MetS was determined according to IDF criteria. RESULTS Acyl-ghrelin levels were significantly lower in obese subjects compared to the control group and lower in obese children with MetS compared to obese subjects without MetS. Obestatin was significantly higher in obese subjects compared to that of the control, but it did not differ significantly among those with or without MetS. Acyl-ghrelin to obestatin ratio was significantly lower in obese subjects compared to that in normal subjects. Acyl-ghrelin showed significant negative and obestatin showed significant positive correlations with body mass index (BMI), BMI Z-score, leptin, insulin, and HOMA-IR. Acyl-ghrelin had a significant negative correlation with MDA as an index of oxidative stress. CONCLUSION Ghrelin is decreased and obestatin is elevated in obesity. Both of these hormones are associated with insulin resistance, and ghrelin is associated with oxidative stress. The balance between ghrelin and obestatin seems to be disturbed in obesity.
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Affiliation(s)
- Maryam Razzaghy-Azar
- Metabolic Disorders Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, 1411715851 Tehran, Iran.
- H. Aliasghar Hospital, Iran University of Medical Sciences, 1449614535 Tehran, Iran.
| | - Mitra Nourbakhsh
- Department of Biochemistry, School of Medicine, Iran University of Medical Sciences, 1449614535 Tehran, Iran.
| | | | - Mona Nourbakhsh
- H. Aliasghar Hospital, Iran University of Medical Sciences, 1449614535 Tehran, Iran.
| | - Davod Ilbeigi
- Department of Biochemistry, School of Medicine, Tehran University of Medical Sciences, 1417614418 Tehran, Iran.
| | - Mohsen Khosravi
- Department of Biochemistry, School of Medicine, Iran University of Medical Sciences, 1449614535 Tehran, Iran.
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12
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Monteiro MEL, Xavier AR, Oliveira FL, Filho PJS, Azeredo VB. Apoptosis induced by a low-carbohydrate and high-protein diet in rat livers. World J Gastroenterol 2016; 22:5165-5172. [PMID: 27298559 PMCID: PMC4893463 DOI: 10.3748/wjg.v22.i22.5165] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2016] [Revised: 03/01/2016] [Accepted: 03/14/2016] [Indexed: 02/06/2023] Open
Abstract
AIM: To determine whether high-protein, high-fat, and low-carbohydrate diets can cause lesions in rat livers.
METHODS: We randomly divided 20 female Wistar rats into a control diet group and an experimental diet group. Animals in the control group received an AIN-93M diet, and animals in the experimental group received an Atkins-based diet (59.46% protein, 31.77% fat, and 8.77% carbohydrate). After 8 wk, the rats were anesthetized and exsanguinated for transaminases analysis, and their livers were removed for flow cytometry, immunohistochemistry, and light microscopy studies. We expressed the data as mean ± standard deviation (SD) assuming unpaired and parametric data; we analyzed differences using the Student’s t-test. Statistical significance was set at P < 0.05.
RESULTS: We found that plasma alanine aminotransferase and aspartate aminotransferase levels were significantly higher in the experimental group than in the control group. According to flow cytometry, the percentages of nonviable cells were 11.67% ± 1.12% for early apoptosis, 12.07% ± 1.11% for late apoptosis, and 7.11% ± 0.44% for non-apoptotic death in the experimental diet group and 3.73% ± 0.50% for early apoptosis, 5.67% ± 0.72% for late apoptosis, and 3.82% ± 0.28% for non-apoptotic death in the control diet group. The mean percentage of early apoptosis was higher in the experimental diet group than in the control diet group. Immunohistochemistry for autophagy was negative in both groups. Sinusoidal dilation around the central vein and small hepatocytes was only observed in the experimental diet group, and fibrosis was not identified by hematoxylin-eosin or Trichrome Masson staining in either group.
CONCLUSION: Eight weeks of an experimental diet resulted in cellular and histopathological lesions in rat livers. Apoptosis was our principal finding; elevated plasma transaminases demonstrate hepatic lesions.
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Preventive effects of citrulline on Western diet-induced non-alcoholic fatty liver disease in rats. Br J Nutr 2016; 116:191-203. [PMID: 27197843 DOI: 10.1017/s0007114516001793] [Citation(s) in RCA: 72] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
A Western diet induces insulin resistance, liver steatosis (non-alcoholic fatty liver disease (NAFLD)) and intestinal dysbiosis, leading to increased gut permeability and bacterial translocation, thus contributing to the progression of NAFLD to non-alcoholic steatohepatitis. In the present study, we sought, in a model of Western diet-induced NAFLD, to determine whether citrulline (Cit), an amino acid that regulates protein and energy metabolism, could decrease Western diet-induced liver injuries, as well as the mechanisms involved. Sprague-Dawley rats were fed a high-fat diet (45 %) and fructose (30 %) in drinking water or a control diet associated with water (group C) for 8 weeks. The high-fat, high-fructose diet (Western diet) was fed either alone (group WD) or with Cit (1 g/kg per d) (group WDC) or an isonitrogenous amount of non-essential amino acids (group WDA). We evaluated nutritional and metabolic status, liver function, intestinal barrier function, gut microbiota and splanchnic inflammatory status. Cit led to a lower level of hepatic TAG restricted to microvesicular lipid droplets and to a lower mRNA expression of CCAAT-enhancer-binding protein homologous protein, a marker of endoplasmic reticulum stress, of pro-inflammatory cytokines Il6 (P<0·05) and Tnfα, and of toll-like receptor 4 (Tlr4) (P<0·05). Cit also improved plasma TAG and insulin levels. In the colon, it decreased inflammation (Tnfα and Tlr4 expressions) and increased claudin-1 protein expression. This was associated with higher levels of Bacteroides/Prevotella compared with rats fed the Western diet alone. Cit improves Western diet-induced liver injuries via decreased lipid deposition, increased insulin sensitivity, lower inflammatory process and preserved antioxidant status. This may be related in part to its protective effects at the gut level.
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Hamed SA, Fathy RA, Radwan ME, Abdellah MM. Fatty liver in adults receiving antiepileptic medications: relationship to the metabolic risks. Expert Rev Clin Pharmacol 2016; 9:617-624. [DOI: 10.1586/17512433.2016.1131123] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2025]
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Cataldi M, di Geronimo O, Trio R, Scotti A, Memoli A, Capone D, Guida B. Utilization of antihypertensive drugs in obesity-related hypertension: a retrospective observational study in a cohort of patients from Southern Italy. BMC Pharmacol Toxicol 2016; 17:9. [PMID: 26980335 PMCID: PMC4793753 DOI: 10.1186/s40360-016-0055-z] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2015] [Accepted: 02/15/2016] [Indexed: 12/28/2022] Open
Abstract
Background Although the pathophysiological mechanisms of arterial hypertension are different in obese and lean patients, hypertension guidelines do not include specific recommendations for obesity-related hypertension and, therefore, there is a considerable uncertainty on which antihypertensive drugs should be used in this condition. Moreover, studies performed in general population suggested that some antihypertensive drugs may increase body weight, glycemia and LDL-cholesterol but it is unclear how this impact on drug choice in clinical practice in the treatment of obese hypertensive patients. Therefore, in order to identify current preferences of practitioners for obesity-related hypertension, in the present work we evaluated antihypertensive drug therapy in a cohort of 129 pharmacologically treated obese hypertensive patients (46 males and 83 females, aged 51.95 ± 10.1 years) that came to our observation for a nutritional consultation. Methods Study design was retrospective observational. Differences in the prevalence of use of the different antihypertensive drug classes among groups were evaluated with χ2 square analysis. Threshold for statistical significance was set at p < 0.05. Results 41.1 % of the study sample was treated with one, 36.4 % with two and the remaining 22.5 % with three or more antihypertensive drugs. In patients under single drug therapy, β-blockers, ACEIs and ARBs accounted each for about 25 % of prescriptions. The prevalence of use of β-blockers was about sixfold higher in females than males. Diuretics were virtually never used in monotherapy regimens but were used in more than 60 % of patients on dual antihypertensive therapy and in all patients assuming three or more drugs. There was no significant difference in the prevalence of use of any of the aforementioned drugs among patients with obesity of type I, II and III or between patients with or without metabolic syndrome. Conclusions Our data show that no first choice protocol seems to be adopted in clinical practice for the treatment of obesity-related hypertension. Importantly, physicians do not seem to differentiate drug use according to the severity of obesity or to the presence of metabolic syndrome or to avoid drugs known to detrimentally affect body weight and metabolic profile in general population.
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Affiliation(s)
- Mauro Cataldi
- Division of Pharmacology, Department of Neuroscience, Reproductive and Odontostomatologic Sciences, Federico II University of Naples, Via Pansini n°5, Naples, 80131, Italy.
| | - Ornella di Geronimo
- Division of Physiology, Department of Clinical Medicine and Surgery, Federico II University of Naples, Naples, Italy
| | - Rossella Trio
- Division of Physiology, Department of Clinical Medicine and Surgery, Federico II University of Naples, Naples, Italy
| | - Antonella Scotti
- Division of Physiology, Department of Clinical Medicine and Surgery, Federico II University of Naples, Naples, Italy
| | - Andrea Memoli
- Division of Nephrology, Department of Public Health, Federico II University of Naples, Naples, Italy
| | - Domenico Capone
- Division of Pharmacology, Department of Neuroscience, Reproductive and Odontostomatologic Sciences, Federico II University of Naples, Via Pansini n°5, Naples, 80131, Italy
| | - Bruna Guida
- Division of Physiology, Department of Clinical Medicine and Surgery, Federico II University of Naples, Naples, Italy
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Singh H, Sidhu S, Chopra K, Khan MU. Hepatoprotective effect of trans-Chalcone on experimentally induced hepatic injury in rats: inhibition of hepatic inflammation and fibrosis. Can J Physiol Pharmacol 2016; 94:879-87. [PMID: 27191034 DOI: 10.1139/cjpp-2016-0071] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
The current study investigated the hepatoprotective effect of trans-Chalcone in carbon tetrachloride (CCl4) and paracetamol (PCM) induced liver damage in rats. Administration of CCl4 and PCM (1 mL/kg, i.p., 3 days, and 2 g/kg, p.o., single dose, respectively) produced hepatic injury. Ponderal changes (percent change in body mass and relative liver mass) and biochemical parameters (serum ALT, AST, ALP, bilirubin) were estimated. The markers of oxidative and nitrosative stress (TBARS, reduced GSH, nitrite and nitrate), hepatic fibrosis (TGF-β1, collagen content), hepatic inflammation (TNF-α), and histopathological study were evaluated. trans-Chalcone (5, 10, and 20 mg/kg, i.p.) was found to be beneficial as demonstrated by significant reversal of liver histology by perceptible reduction of inflammatory cell infiltration with regenerative changes in hepatocytes. Improvement in percent change in body mass and significant reduction in relative liver mass were observed. Marked reduction in serum levels of ALT, AST, ALP, and bilirubin were noted. Decreases in TBARS and nitrites and nitrates and increases in reduced GSH levels were noted. Hepatic fibrosis and inflammation were significantly decreased. The findings indicate a novel hepatoprotective role for trans-Chalcone by improving hepatic injury by possible actions such as anti-oxidant, anti-nitrosative, anti-fibrotic, and anti-inflammatory. Hence, it can be used as promising hepatoprotective agent.
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Affiliation(s)
- Harsimran Singh
- a Department of Research Innovations and Consultancy, IKG Punjab Technical University, Kapurthala, Punjab 144 601, India.,d Sri Sai College of Pharmacy, Badhani, Pathankot, Punjab 145 001, India
| | - Shabir Sidhu
- b Department of Life Sciences, Punjab Institute of Technology, IKG Punjab Technical University Kapurthala, Punjab 144 601, India
| | - Kanwaljit Chopra
- c Pharmacology Research Laboratory, University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Study, Panjab University, Chandigarh 160 014, India
| | - M U Khan
- d Sri Sai College of Pharmacy, Badhani, Pathankot, Punjab 145 001, India
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Cheng PN, Chiu YC, Chiu HC, Chien SC. The Application of Liver Stiffness Measurement in Residents Without Overt Liver Diseases Through a Community-Based Screening Program. Medicine (Baltimore) 2016; 95:e3193. [PMID: 27015215 PMCID: PMC4998410 DOI: 10.1097/md.0000000000003193] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
The application of liver stiffness measurement (LSM) by transient elastography (TE) in general population remains to clarify. This cohort study aimed to examine the usefulness of TE and to identify factors associated with significant liver fibrosis in community-based population.We conducted a hepatitis screening program in 2 remote villages of Southern Taiwan. All residents participated voluntarily and received questionnaire evaluation, blood tests, abdominal sonography, and LSM by TE. Residents with any one of following criteria including hepatitis B virus infection, hepatitis C virus infection, more than moderate alcohol drinking, and failure to obtain valid or reliable LSM were excluded.There were 831 residents participated in program. The valid and reliable LSM were obtained in 98.3% and 96.3% of residents, respectively. Finally, a total of 559 residents including 283 residents with nonalcoholic steatotic fatty liver disease (NAFLD) were enrolled for analysis. The mean liver stiffness was 4.9 ± 1.9 kPa. The liver stiffness increased in residents with diabetes mellitus (DM), higher body mass index (BMI), hypertension, abnormal waist-hip circumference ration (WHR), higher waist circumference (WC), and presence of fatty liver. Higher body weight, higher BMI, higher WC, abnormal WHR, abnormal aspartate aminotransferase (AST), abnormal alanine aminotransferase (ALT), and DM were the factors associated with significant fibrosis (liver stiffness ≥7 kPa) in either all participants or NAFLD residents. As determined by multivariate analysis, abnormal AST values and DM were the 2 independent factors in all participants (abnormal AST: OR 3.648, 95% CI 1.134-11.740, P = 0.03; DM: OR 2.882, 95% CI 1.282-6.478, P = 0.01) and in residents with NAFLD (abnormal AST: OR 4.197, 95% CI 1.154-15.262, P = 0.03; DM: OR 3.254, 95% CI 1.258-8.413, P = 0.02).LSM by TE is a useful screening tool in community. In residents, who were absence of chronic hepatitis virus infection or consumed less than moderate alcohol drinking, exhibited DM or abnormal AST values may consider a substantial group with significant fibrosis in community.
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Affiliation(s)
- Pin-Nan Cheng
- From the Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
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Abstract
Periodontal disease is a chronic inflammatory disease of the jaws and is more prevalent in obesity. Local and systemic oxidative stress may be an early link between periodontal disease and obesity. The primary aim of this study was to detect whether increased periodontal disease susceptibility in obese individuals is associated with local and systemic oxidative stress. Accordingly; we analyzed periodontal status and systemic (serum) and local (gingival crevicular fluid [GCF]) oxidative status markers in young obese women in comparison with age-matched lean women.Twenty obese and 20 lean women participated. Periodontal condition was determined by clinical periodontal indices including probing depth, clinical attachment level, gingival index, gingival bleeding index, and plaque index. Anthropometric, hormonal, and metabolic measurements were also performed. Blood and GCF sampling was performed at the same time after an overnight fasting. Serum and GCF total antioxidant capacity (TAOC), and total oxidant status (TOS) levels were determined, and oxidative stress index (OSI) was calculated.Clinical periodontal analyses showed higher gingival index and gingival bleeding index in the obese group (P = 0.001 for both) with no significant difference in probing depth, clinical attachment level, and plaque index between the obese and the lean women. Oxidant status analyses revealed lower GCF and serum TAOC, and higher GCF and serum OSI values in the obese women (P < 0.05 for all). GCF TOS was higher in the obese women (P < 0.05), whereas there was a nonsignificant trend for higher serum TOS in obese women (P = 0.074). GCF TAOC values showed a negative correlation with body mass index, whereas GCF OSI was positively correlated with fasting insulin and low-density lipoprotein-cholesterol levels (P < 0.05 for all). Clinical periodontal indices showed significant correlations with body mass index, insulin, and lipid levels, and also oxidant status markers.Our results suggest that young obese, otherwise healthy, women show findings of early periodontal disease (gingival inflammation) compared with age-matched healthy lean women, and that local/periodontal oxidative stress generated by obesity seems to be associated with periodontal disease.
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Affiliation(s)
- Erhan Dursun
- From the Department of Periodontology (ED, FAA, TG), Faculty of Dentistry; Division of Endocrinology and Metabolism (NC, BOY), Department of Internal Medicine, Faculty of Medicine, Hacettepe University; and Department of Biochemistry (OE), Faculty of Medicine, Yıldırım Beyazıt University, Ankara, Turkey
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Jang YS, Wang Z, Lee JM, Lee JY, Lim SS. Screening of Korean Natural Products for Anti-Adipogenesis Properties and Isolation of Kaempferol-3-O-rutinoside as a Potent Anti-Adipogenetic Compound from Solidago virgaurea. Molecules 2016; 21:molecules21020226. [PMID: 26901177 PMCID: PMC6273009 DOI: 10.3390/molecules21020226] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2015] [Revised: 02/06/2016] [Accepted: 02/09/2016] [Indexed: 11/16/2022] Open
Abstract
In this study, the anti-adipogenetic activity of 300 plant extracts was investigated using an Oil Red O staining assay in a 3T3-L1 cell line. Our results indicate that three plants, including the stem and leaf of Physalis angulata, the whole grass of Solidago virgaurea, and the root of Dioscorea nipponica, produced over 90% inhibition of adipogenesis. Kaempferol-3-O-rutinoside, which demonstrated a 48.2% inhibitory effect on adipogenesis without cytotoxicity, was isolated from the butanol layer of a water extract of S. virgaurea guided by the anti-adipogenesis assay in 3T3-L1. PPAR-γ and C/EBPα expression levels were determined using western blot, and our results indicate that kaempferol-3-O-rutinoside has a strong anti-adipogenic effect in 3T3-L1 cells through the suppression of increases in PPAR-γ and C/EBPα expression.
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Affiliation(s)
- Young Soo Jang
- Department of Food Science and Nutrition, Hallym University, Okchon-dong, Chuncheon, Gangwon-do 200-702, Korea.
| | - Zhiqiang Wang
- Department of Food Science and Nutrition, Hallym University, Okchon-dong, Chuncheon, Gangwon-do 200-702, Korea.
| | - Jeong-Min Lee
- Department of Boichemistry, Hallym University Medical School, Okchon-dong, Chuncheon, Gangwon-do 200-702, Korea.
| | - Jae-Young Lee
- Department of Boichemistry, Hallym University Medical School, Okchon-dong, Chuncheon, Gangwon-do 200-702, Korea.
- Institute of Natural Medicine, Hallym University, Okchon-dong, Chuncheon, Gangwon-do 200-702, Korea.
| | - Soon Sung Lim
- Department of Food Science and Nutrition, Hallym University, Okchon-dong, Chuncheon, Gangwon-do 200-702, Korea.
- Institute of Natural Medicine, Hallym University, Okchon-dong, Chuncheon, Gangwon-do 200-702, Korea.
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Effect of Folic Acid, Betaine, Vitamin B₆, and Vitamin B12 on Homocysteine and Dimethylglycine Levels in Middle-Aged Men Drinking White Wine. Nutrients 2016; 8:nu8010034. [PMID: 26771632 PMCID: PMC4728648 DOI: 10.3390/nu8010034] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2015] [Revised: 01/04/2016] [Accepted: 01/06/2016] [Indexed: 11/17/2022] Open
Abstract
Moderate regular consumption of alcoholic beverages is believed to protect against atherosclerosis but can also increase homocysteine or dimethylglycine, which are putative risk factors for atherosclerosis. We aimed (1) to investigate the effect of alcohol consumption on vitamins and several metabolites involved in one-carbon metabolism; and (2) to find the most effective way of decreasing homocysteine during moderate alcohol consumption. Methods: Male volunteers (n = 117) were randomly divided into five groups: the wine-only group (control, 375 mL of white wine daily for one month) and four groups combining wine consumption with one of the supplemented substances (folic acid, betaine, and vitamins B12 or B6). Significant lowering of homocysteine concentration after the drinking period was found in subjects with concurrent folate and betaine supplementation. Vitamin B12 and vitamin B6 supplementation did not lead to a statistically significant change in homocysteine. According to a multiple linear regression model, the homocysteine change in the wine-only group was mainly determined by the interaction between the higher baseline homocysteine concentration and the change in dimethylglycine levels. Folate and betaine can attenuate possible adverse effects of moderate alcohol consumption. Dimethylglycine should be interpreted together with data on alcohol consumption and homocysteine concentration.
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Hamed SA, Fathy RA, Radwan ME, Abdellah MM. Fatty liver in adults receiving antiepileptic medications: relationship to the metabolic risks. Expert Rev Clin Pharmacol 2016; 9:617-624. [PMID: 26652506 DOI: org/10.1586/17512433.2016.1131123] [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: 11/08/2022]
Abstract
This study aimed to determine the frequency of fatty liver disease (FLD) induced by antiepileptic drugs (AEDs) and its relationship to the metabolic profile. This study included 130 patients (valproate or VPA = 75; carbamazepine or CBZ = 40; lamotrigine or LTG = 15). Liver ultrasonography (US) was done. Serum lipids, uric acid, free fatty acids (FFAs), glucose, insulin and leptin were measured. Compared to controls and patients on CBZ or LTG, higher BMI; TC, TG, LDL-c, uric acid, FFAs, glucose, insulin and leptin concentrations and enlarged liver lobes volume and span and insulin resistance (45%) were reported with VPA. With FLD, significant correlations were reported between BMI with leptin (r = 0.390;p < 0.01), insulin (r = 0.655;p < 0.001) and FFAs (r = 0.570;p < 0.001) and insulin with leptin (r = 0.355;p < 0.01). In multivariate analysis, with FLD, liver span was correlated with BMI (OR:4.50;95%CI:1.54-13.3,p = 0.01) and leptin concentrations (OR:2.55;95%CI:1.04-6.27,p = 0.045). We conclude that VPA therapy is a risk for FLD and is correlated with the associated adverse metabolic profile.
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Affiliation(s)
- Sherifa A Hamed
- a Department of Neurology and Psychiatry , Assiut University Hospital , Assiut , Egypt
| | - Refaat A Fathy
- b Department of Internal Medicine , Assiut University Hospital , Assiut , Egypt
| | - Moustafa E Radwan
- c Department of Radiology , Assiut University Hospital , Assiut , Egypt
| | - Mostafa M Abdellah
- d Department of Pharmacology, Faculty of Medicine , Assiut University Hospital , Assiut , Egypt
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Tarantino G, Finelli C. Lipids, Low-Grade Chronic Inflammation and NAFLD. HANDBOOK OF LIPIDS IN HUMAN FUNCTION 2016:731-759. [DOI: 10.1016/b978-1-63067-036-8.00028-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Di Naso FC, Porto RR, Fillmann HS, Maggioni L, Padoin AV, Ramos RJ, Mottin CC, Bittencourt A, Marroni NAP, de Bittencourt PIH. Obesity depresses the anti-inflammatory HSP70 pathway, contributing to NAFLD progression. Obesity (Silver Spring) 2015; 23:120-9. [PMID: 25292174 DOI: 10.1002/oby.20919] [Citation(s) in RCA: 76] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2014] [Accepted: 09/12/2014] [Indexed: 12/15/2022]
Abstract
OBJECTIVES To evaluate whether reduced activity of the anti-inflammatory HSP70 pathway correlates with nonalcoholic fatty liver disease (NAFLD) progression and with markers of oxidative stress because obesity activates inflammatory JNKs, whereas HSP70 exerts the opposite effect. METHODS Adult obese patients (N = 95) undergoing bariatric surgery were divided into steatosis (ST), steatohepatitis (SH), and fibrosis (SH+F) groups. The levels of HSP70, its major transcription factor, HSF1, and JNKs were assessed by immunoblotting hepatic and visceral adipose tissue; data were confirmed by immunohistochemistry. Plasma biochemistry (lipids, HbA1c , HOMA, hepatic enzymes, and redox markers) was also evaluated. RESULTS In both liver and adipose tissue, decreased HSP70 levels, paralleled by similar reductions in HSF1 and reduced plasma antioxidant enzyme activities, correlated with insulin resistance and with NAFLD progression (expression levels were as follows: ST > SH > SH + F). The immunohistochemistry results suggested Kupffer cells as a site of HSP70 inhibition. Conversely, JNK1 content and phosphorylation increased. CONCLUSIONS Decreased HSF1 levels in the liver and fat of obese patients correlated with impairment of HSP70 in an NAFLD stage-dependent manner. This impairment may affect HSP70-dependent anti-inflammation, with consequent oxidative stress and insulin resistance in advanced stages of NAFLD. Possible causal effects of fat cell senescence are discussed.
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Affiliation(s)
- Fábio Cangeri Di Naso
- Laboratory of Physiology and Experimental Hepatology, Porto Alegre Clinics Hospital, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
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Wang Y, Li YY, Nie YQ, Zhou YJ, Cao CY, Xu L. Association between metabolic syndrome and the development of non-alcoholic fatty liver disease. Exp Ther Med 2013; 6:77-84. [PMID: 23935723 PMCID: PMC3735568 DOI: 10.3892/etm.2013.1090] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2013] [Accepted: 04/10/2013] [Indexed: 02/06/2023] Open
Abstract
The aim of this study was to examine the effects of metabolic syndrome (MS) and the number of MS components on the development of non-alcoholic fatty liver disease (NAFLD). A total of 1,343 males and 574 females aged ≥50 years without NAFLD at baseline were included. Information on lifestyle, including alcohol use and personal history, was collected by face-to-face interviews. Biochemical parameters were assayed using fasting blood samples. NAFLD was diagnosed by abdominal ultrasonography. During follow-up at an average of 4.8 years, 223 patients developed NAFLD. Following adjustment for multiple covariates, age was an independent protective predictor [hazard ratio (HR), 0.96; 95% confidence interval (CI), 0.95-0.98], while the independent risk predictors were obesity (HR, 2.81; 95% CI, 2.14-3.69), higher triglycerides (HR, 2.56; 95% CI, 1.95-3.32) and alanine aminotransferase (HR, 1.004; 95% CI, 1.000-1.008). Participants with a diagnosis of MS had a significantly increased risk of developing NAFLD (HR, 3.17; 95% CI, 2.42-4.14). A greater number of MS components was significantly associated with a higher risk of NAFLD (all adjusted P for trend <0.001). Compared with those without any components of MS, participants with only one component of MS had a 3.6-fold higher risk of developing NAFLD (adjusted HR, 3.64; 95% CI, 1.50-8.88). The diagnosis and the number of components of MS were prospectively associated with the risk of developing NAFLD. Even in those with only one component of MS, the risk increased by 2.6-fold compared with that for the individuals without any components, suggesting a beneficial effect of intervention at the very early stage of MS on the prevention of NAFLD.
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Affiliation(s)
- Yi Wang
- Departments of Infectious Disease, Guangzhou Medical University, Guangzhou, Guangdong 510180
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Tarantino G. Is Assessing the Presence of NASH by Liver Histology or Surrogate Markers Always Advisable? HEPATITIS MONTHLY 2013; 13:e7560. [PMID: 23610586 PMCID: PMC3631528 DOI: 10.5812/hepatmon.7560] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 08/02/2012] [Accepted: 09/28/2012] [Indexed: 12/11/2022]
Affiliation(s)
- Giovanni Tarantino
- Department of Clinical and Experimental Medicine, School of Naples, Federico II University Medical, Naples, Italy
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Seo HI, Cho YK, Lee WY, Rhee EJ, Sung KC, Kim BS, Son BH, Shin JH, Joo KJ, Hong HP, Chae SW, Jin W. Which metabolic syndrome criteria best predict the presence of non-alcoholic fatty liver disease? Diabetes Res Clin Pract 2012; 95:19-24. [PMID: 21908065 DOI: 10.1016/j.diabres.2011.08.013] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2011] [Revised: 08/05/2011] [Accepted: 08/15/2011] [Indexed: 01/14/2023]
Abstract
AIMS To know which MS criteria best predict the presence of NAFLD and the prevalences of metabolic syndrome (MS) and non-alcoholic fatty liver disease (NAFLD) diagnosed ultrasonographically among pre-diabetic and diabetic subjects based on three different MS criteria (IDF, ATP III, WHO). METHODS Subjects were screened and those with a fasting serum glucose level ≥100 mg/dL were further tested with a 75 g oral glucose tolerance test. And those who were newly diagnosed as having pre-diabetes or diabetes were evaluated for MS and NAFLD. We compared the risk ratios of NAFLD among three MS criteria using multivariate and multiple logistic regression analyses. RESULTS A total of 1365 subjects (977 males, mean age 48.4±9.5 years) were analyzed. The WHO criteria produced the highest prevalence of MS in both the pre-diabetic (49.8%) and diabetic (58.9%) groups. The IDF criteria produced the highest odds ratio for NAFLD in both pre-diabetic (3.89 [95% CI 2.75-5.51]) and diabetic (5.53 [95% CI 3.21-9.52]) groups. CONCLUSIONS The prevalence of MS depends on the set of diagnostic criteria used. IDF criteria best predicts the presence of NAFLD. The presence of NAFLD should be considered as a component of the diagnostic criteria for MS.
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Affiliation(s)
- Hyun Il Seo
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
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Tarantino G, Scopacasa F, Colao A, Capone D, Tarantino M, Grimaldi E, Savastano S. Serum Bcl-2 concentrations in overweight-obese subjects with nonalcoholic fatty liver disease. World J Gastroenterol 2011; 17:5280-5288. [PMID: 22219597 PMCID: PMC3247692 DOI: 10.3748/wjg.v17.i48.5280] [Citation(s) in RCA: 58] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2011] [Revised: 06/27/2011] [Accepted: 10/27/2011] [Indexed: 02/06/2023] Open
Abstract
AIM To shed some light on the relationship between anti-apoptotic serum Bcl-2 concentrations and metabolic status, anthropometric parameters, inflammation indices, and non-alcoholic fatty liver disease severity were investigated in 43 young individuals with fatty liver (FL) and 41 with nonalcoholic steatohepatitis (NASH). METHODS Circulating levels of Bcl-2 were detected in 84 patients with ultrasonographic findings of "bright liver" and/or hyper-transaminasemia of unknown origin and/or increase in γ-glutamyl-transpeptidase (γ-GT) strictly in the absence of other acute or chronic liver disease, whose age was not advanced, who gave consent to liver biopsy and were then divided on the basis of the histological results into two groups (43 with FL and 41 with NASH). Twenty lean subjects, apparently healthy and young, were chosen as controls. RESULTS Serum Bcl-2 concentrations were significantly higher in the FL group than in the NASH group. Insulin resistance and γ-GT activity were significantly higher in NASH subjects. Apoptotic hepatocytes were significantly more numerous in NASH patients. NASH patients presented with larger spleens and augmented C-reactive protein (CRP) concentrations than healthy subjects. Steatosis grade at histology was similar in both NASH and FL populations. The number of apoptotic cells was significantly related to anti-apoptotic Bcl-2 protein values in FL patients. Bcl-2 serum levels positively correlated to body mass index (BMI) values (P ≤ 0.0001) but not to age of the population. Triglycerides/HDL ratio correlated well to waist circumference in males (P = 0.0008). γ-GT activity was associated with homeostatic metabolic assessment (HOMA) (P = 0.0003) and with serum ferritin (P = 0.02). Bcl-2 concentrations were not related to either spleen size or CRP values. NASH patients presented a weak negative correlation between lobular inflammation and Bcl-2 levels. A prediction by low values of serum Bcl-2 towards a greater presence of metabolically unhealthy overweight/obese patients (MUOs) was evidenced. HOMA, BMI and uric acid, in that sequence, best predicted serum Bcl-2 concentrations. CONCLUSION MUOs could be detected by Bcl-2 levels. By favoring the life span of hepatocytes, and enhancing triglyceride formation, the anti-apoptotic process inhibits free fatty acids toxicity in FL.
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Ciupińska-Kajor M, Hartleb M, Kajor M, Kukla M, Wyleżoł M, Lange D, Liszka L. Hepatic angiogenesis and fibrosis are common features in morbidly obese patients. Hepatol Int 2011; 7:233-40. [PMID: 23519653 PMCID: PMC3601246 DOI: 10.1007/s12072-011-9320-9] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2011] [Accepted: 11/10/2011] [Indexed: 02/08/2023]
Abstract
Background A mass of visceral adipose tissue is one of the most important determinants of progressive liver injury in nonalcoholic fatty liver disease (NAFLD). In accordance, nonalcoholic steatohepatitis (NASH) and fibrosis are believed to occur more commonly in morbidly obese patients compared with nonobese NAFLD patients. Aim of the study Comparative analysis of NAFLD histopathologic features and angiogenesis activity in morbidly obese and nonobese subjects. Materials and methods Biopsy samples from 40 severely obese (BMI ≥40 kg m−2) and 30 nonobese (BMI ≤30 kg m−2) NAFLD patients were examined. Kleiner’s classification was used to diagnose NASH by grading steatosis, cytoplasmatic ballooning of hepatocytes, and lobular inflammation. The severity of fibrosis was evaluated according to the liver fibrosis staging system. Qualitative and quantitative immunohistochemical analyses of VEGF A, Flk-1, and CD34 were performed to study angiogenesis and the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) method was used to study hepatocyte apoptosis. Results Severely obese patients did not differ from nonobese patients with respect to age and sex distribution. NASH was diagnosed in nine (22.5%) severely obese patients and in seven (23.3%) nonobese patients. Fibrosis was more common in morbidly obese patients (82.5 vs. 43.5%, χ² = 11.71, p = 0.003) and was not associated with NASH. Moreover, the severity of fibrosis was greater in obese patients, as advanced fibrosis (bridging fibrosis and cirrhosis) occurred in six (15%) severely obese patients and in two (6.7%) nonobese patients. In morbidly obese individuals, angiogenesis was independent of NASH and was activated at the stage of simple steatosis. In severe obesity, there was a positive relationship between the stage of fibrosis and angiogenic activity. Conclusion In severely obese patients, fibrosis is probably promoted by mechanisms independent of NASH. In these patients, angiogenesis is activated early in the natural history of NAFLD and correlates with the severity of fibrosis.
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Tarantino G, Caputi A. JNKs, insulin resistance and inflammation: A possible link between NAFLD and coronary artery disease. World J Gastroenterol 2011; 17:3785-3794. [PMID: 21987620 PMCID: PMC3181439 DOI: 10.3748/wjg.v17.i33.3785] [Citation(s) in RCA: 113] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2010] [Revised: 02/19/2011] [Accepted: 02/26/2011] [Indexed: 02/06/2023] Open
Abstract
The incidence of obesity has dramatically increased in recent years. Consequently, obesity and associated disorders such as nonalcoholic fatty liver disease constitute a serious problem. Therefore, the contribution of adipose tissue to metabolic homeostasis has become a focus of interest. In this review, we discuss the latest discoveries that support the role of lipids in nonalcoholic fatty liver disease. We describe the common mechanisms (c-Jun amino-terminal kinases, endoplasmic reticulum stress, unfolded protein response, ceramide, low-grade chronic inflammation) by which lipids and their derivatives impair insulin responsiveness and contribute to inflammatory liver and promote plaque instability in the arterial wall. Presenting the molecular mechanism of lipid activation of pro-inflammatory pathways, we attempt to find a link between nonalcoholic fatty liver disease, metabolic syndrome and cardiovascular diseases. Describing the common mechanisms by which lipid derivatives, through modulation of macrophage function, promote plaque instability in the arterial wall, impair insulin responsiveness and contribute to inflammatory liver and discussing the molecular mechanism of lipid activation of pro-inflammatory pathways, the key roles played by the proliferator-activated receptor and liver X receptor α, nuclear receptors-lipid sensors that link lipid metabolism and inflammation, should be emphasized. Further studies are warranted of anti-inflammatory drugs such as aspirin, anti-interleukin-6 receptors, immune-modulators (calcineurin inhibitors), substances enhancing the expression of heat shock proteins (which protect cells from endoplasmic reticulum stress-induced apoptosis), and anti- c-Jun amino-terminal kinases in well-designed trials to try to minimize the high impact of these illnesses, and the different expressions of the diseases, on the whole population.
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Tarantino G, Savastano S, Colao A, Polichetti G, Capone D. Urinary excretion of 5-hydroxy-3-indoleacetic acid in dystimic/depressed, adult obese women: what correlations to hepatic steatosis? Int J Immunopathol Pharmacol 2011; 24:769-779. [PMID: 21978708 DOI: 10.1177/039463201102400323] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
The synthesis of serotonin at CNS level is influenced by diet. Moreover, insulin resistance is associated with lower serotonin levels. Visceral obesity, strictly linked to hepatic steatosis is specifically associated with mild to severe somatic affective-depressive symptom clusters. Previous data support the view that depression involves serotonergic systems, reflecting low levels of urinary 5- hydroxy-3-indoleacetic acid (5-HIAA). The 24-h urinary excretion of 5-HIAA was evaluated in 76 dystimic/depressed, obese/overweight females, divided into two groups, i.e., on a hyper-caloric diet, associated with a life style characterized by leisure time sedentary behavior (LTSB, 35 women), or on a normo-caloric diet, assisted by program-based strategies aimed at promoting physical activity participation (PAP, 41 women). Beck Depression Inventory (BDI) was carried out to score the severity of dystimia/depression. Anthropometric measures, metabolic indices, severity of hepatic steatosis at sonography and HOMA were studied. Urinary levels of 5-HIAA in controls and PAP groups were comparable with a great overlap, while in the LTSB group the urinary excretion of 5-HIAA was significantly reduced in respect to that of the PAP group and obviously compared to that of the control group, 3.4±1.4 mg/L versus 6.2±2.7 mg/L and 6.4±2.6 mg/L, respectively, ANOVA test, P= 0.001. Among metabolic indices, cholesterol, HDL-cholesterol, triglycerides and uric acid were not able to predict urinary concentrations of 5-HIAA, which were not associated with hepatic steatosis; vice versa, ferritin levels, and mainly HOMA values, were independent predictors of the urinary excretion of 5-HIAA (β=0.235 and 0.45, respectively). Dystimia/depression severity was negatively predicted by urinary 5-HIAA levels in the sense that the highest BDI values were forecast by the lowest values of urinary 5-HIAA (β= -0.72).The importance of measuring the 24-h urinary excretion of 5-HIAA in follow-ups could rely on a method simultaneously mirroring the well-being status, the adherence to physical activity, which leads to improved insulin sensitivity, and the eating habits acquired by dystimic/depressed overweight/obese patients. In contrast, the significance of the urinary 5-HIAA is reduced in evaluating the severity of hepatic steatosis, likely because it is a structured process.
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Affiliation(s)
- Giovanni Tarantino
- Department of Clinical and Experimental Medicine, Federico II University Medical School of Naples, Italy.
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Fierbinteanu-Braticevici C, Dina I, Petrisor A, Tribus L, Negreanu L, Carstoiu C. Noninvasive investigations for non alcoholic fatty liver disease and liver fibrosis. World J Gastroenterol 2010; 16:4784-4791. [PMID: 20939106 PMCID: PMC2955247 DOI: 10.3748/wjg.v16.i38.4784] [Citation(s) in RCA: 49] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2010] [Revised: 06/28/2010] [Accepted: 07/05/2010] [Indexed: 02/07/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) includes a spectrum of diseases that have insulin resistance in common and are associated with metabolic conditions such as obesity, type 2 diabetes mellitus, and dyslipidemia. NAFLD ranges from simple liver steatosis, which follows a benign course, to nonalcoholic steatohepatitis (NASH), a more severe entity, with necroinflammation and fibrosis, which can progress to cryptogenic cirrhosis and end-stage liver disease. Liver biopsy remains the gold standard for evaluating the degree of hepatic necroinflammation and fibrosis; however, several noninvasive investigations, such as serum biomarkers, have been developed to establish the diagnosis and also to evaluate treatment response. These markers are currently neither available in all centers nor validated in extensive studies. Examples include high-sensitivity C reactive protein and plasma pentraxin 3, which are associated with extensive liver fibrosis in NASH. Interleukin-6 correlates with inflammation, and cytokeratin-18 represents a marker of hepatocyte apoptosis (prominent in NASH and absent in simple steatosis). Tissue polypeptide specific antigen seems to have a clinical utility in the follow-up of obese patients with NASH.
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Tarantino G, Savastano S, Colao A. Hepatic steatosis, low-grade chronic inflammation and hormone/growth factor/adipokine imbalance. World J Gastroenterol 2010; 16:4773-4783. [PMID: 20939105 PMCID: PMC2955246 DOI: 10.3748/wjg.v16.i38.4773] [Citation(s) in RCA: 162] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2010] [Revised: 06/15/2010] [Accepted: 06/22/2010] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD), a further expression of metabolic syndrome, strictly linked to obesity and diabetes mellitus, is characterized by insulin resistance (IR), elevated serum levels of free fatty acids and fatty infiltration of the liver, which is known as hepatic steatosis. Hepatocyte apoptosis is a key feature of this disease and correlates with its severity. Free-fatty-acid-induced toxicity represents one of mechanisms for the pathogenesis of NAFLD and hormones, growth factors and adipokines influence also play a key role. This review highlights the various pathways that contribute to the development of hepatic steatosis. Circulating concentrations of inflammatory cytokines are reckoned to be the most important factor in causing and maintaining IR. Low-grade chronic inflammation is fundamental in the progression of NAFLD toward higher risk cirrhotic states.
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Ferreira VSG, Pernambuco RB, Lopes EP, Morais CN, Rodrigues MC, Arruda MJ, Silva LME, Vilar L. Frequency and risk factors associated with non-alcoholic fatty liver disease in patients with type 2 diabetes mellitus. ARQUIVOS BRASILEIROS DE ENDOCRINOLOGIA E METABOLOGIA 2010; 54:362-8. [PMID: 20625647 DOI: 10.1590/s0004-27302010000400004] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/22/2009] [Accepted: 03/03/2010] [Indexed: 12/15/2022]
Abstract
OBJECTIVE To evaluate the frequency of non-alcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (DM2) and to describe its risk factors. SUBJECTS AND METHODS Blood samples of 78 patients were collected for assessment of glycemic and lipid profile, liver enzymes, TNF-alpha and HOMA-IR. The diagnosis of NAFLD was established by ultrasound. RESULTS NAFLD was observed in 42% of patients who had greater BMI (p < 0.001), and frequency of hypertension (p < 0.001). Metabolic syndrome was more frequent in those with NAFLD (p = 0.019). The levels of aspartate, alanine aminotransferase, gamma-glutamyl transpeptidase, uric acid, TNF-alpha, insulin and HOMA-IR were significantly higher in patients with NAFLD than those without NAFLD. CONCLUSION Almost half of patients with DM2 were found to have NAFLD, and they have more elevated BMI, as well as higher levels of aminotransferases, gamma-GT, uric acid, TNF-alpha, insulin and HOMA-IR than subjects without NAFLD.
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Affiliation(s)
- Vera S G Ferreira
- Departamento de Medicina Clínica, Universidade Federal de Pernambuco, Recife, PE, Brazil.
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Zingarelli B, Chima R, O'Connor M, Piraino G, Denenberg A, Hake PW. Liver apoptosis is age dependent and is reduced by activation of peroxisome proliferator-activated receptor-gamma in hemorrhagic shock. Am J Physiol Gastrointest Liver Physiol 2010; 298:G133-41. [PMID: 19926821 PMCID: PMC2806104 DOI: 10.1152/ajpgi.00262.2009] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
A clinical observation in pediatric and adult intensive care units is that the incidence of multiple organ failure in pediatric trauma victims is lower than in adult patients. However, the molecular mechanisms are not yet defined. Recent experimental studies have shown that the nuclear peroxisome proliferator-activated receptor-gamma (PPARgamma) modulates the inflammatory process. In this study, we hypothesized that severity of liver injury may be age dependent and PPARgamma activation may provide beneficial effects. Hemorrhagic shock was induced in anesthetized young (3-5 mo old) and mature male Wistar rats (11-13 mo old) by withdrawing blood to a mean arterial blood pressure of 50 mmHg. After 3 h, rats were rapidly resuscitated with shed blood. Animals were euthanized 3 h after resuscitation. In mature rats, liver injury appeared more pronounced compared with young rats and was characterized by marked hepatocyte apoptosis, extravasation of erythrocytes, and accumulation of neutrophils. The ratio between the antiapoptotic protein Bcl-2 and the proapoptotic protein BAX was lower, whereas activity of caspase-3, the executioner of apoptosis, was higher in liver of mature rats compared with young rats. Plasma alanine aminotransferase levels were not different between the two age groups. This heightened liver apoptosis was associated with a significant downregulation of PPARgamma DNA binding in mature rats compared with young rats. Treatment with the PPARgamma ligand ciglitazone significantly reduced liver apoptosis in mature rats. Our data suggest that liver injury after severe hemorrhage is age dependent and PPARgamma activation is a novel hepatoprotective mechanism.
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Affiliation(s)
- Basilia Zingarelli
- Division of Critical Care Medicine, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave., Cincinnati, OH 45229, USA.
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Yuan WP, Liu B, Liu CH, Wang XJ, Zhang MS, Meng XM, Xia XK. Antioxidant activity of chito-oligosaccharides on pancreatic islet cells in streptozotocin-induced diabetes in rats. World J Gastroenterol 2009; 15:1339-45. [PMID: 19294763 PMCID: PMC2658843 DOI: 10.3748/wjg.15.1339] [Citation(s) in RCA: 47] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the antioxidant activity of chito-oligosaccharides (COSs) on pancreatic islet cells in diabetic rats induced by streptozotocin.
METHODS: The antioxidant effect of COSs on pancreatic islet cells was detected under optical microscopy and with colorimetric assay and gel electrophoresis. The activities of glutathione peroxidase and superoxide dismutase, total antioxidant capacity, and content of malondialdehyde in serum and tissue slices of pancreas were examined after 60 d to determine the effect of COSs in streptozotocin-induced diabetes in rats.
RESULTS: COSs can prohibit the apoptosis of pancreatic islet cells. All concentrations of COSs can improve the capability of total antioxidant capacity and activity of superoxide dismutase and decrease the content of malondialdehyde drastically. Morphological investigation in the pancreas showed that COSs have resulted in the reduction of islets, loss of pancreatic cells, and nuclear pyknosis of pancreatic cells.
CONCLUSION: COSs possess various biological activities and can be used in the treatment of diabetes mellitus.
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Non-alcoholic Steatohepatitis Induces a Decrease in the Levels of S-100b in the Rat Brain. NEUROPHYSIOLOGY+ 2009. [DOI: 10.1007/s11062-009-9051-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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