Liver Disease In Metabolic Syndrome Research Articles

Combination of a Glucagon-Like Peptide 1 Analog and a Sodium-Glucose Cotransporter 2 Inhibitor Improves Lipid Metabolism Compared to the Monotherapies in Experimental Metabolic Syndrome

Background: Obesity is a risk factor for insulin resistance, dyslipidemia, fatty liver disease, and all disorders associated with metabolic syndrome. Here we evaluated the association of the glucagon-like peptide 1 (GLP-1) analog, liraglutide, and the sodium-glucose cotransporter-2 (SGLT-2) inhibitor, canagliflozin, on the improvement of metabolic syndrome symptoms in a high-fat diet (HFD)-induced obesity rat model. Methods: Male Wistar rats received either a control diet or HFD ad libitum for 5 months. After 4 months of diet, HFD rats were randomly divided into four experimental groups (HFD, HFD + liraglutide, HFD + canagliflozin, and HFD + liraglutide + canagliflozin). Treatment groups received liraglutide (100 µg/kg) and/or canagliflozin (10 mg/kg) once daily for one month. Body mass and food intake were monitored throughout the experiment. An oral glucose tolerance test, biochemical parameters, epididymal and liver fat, and adipocyte morphology were assessed after the treatment period. Results: Rats on the HFD developed obesity, glucose intolerance, dyslipidemia, and fatty liver. Liraglutide reduced food intake and body weight, normalized the lipid profile, and reduced abdominal and liver fat. Canagliflozin slightly reduced body mass and improved glucose tolerance and dyslipidemia. The combination therapy was more effective than the monotherapies in normalizing the lipid profile. Conclusions: The combination of liraglutide and canagliflozin was more effective than the monotherapies in improving dyslipidemia and liver fat. These results indicate that the combination of GLP-1 receptor agonists and SGLT-2 inhibitors is a promising therapeutic strategy to treat dyslipidemia, and possibly prevent fatty liver disease in metabolic syndrome and obese patients. J Endocrinol Metab. 2022;12(6):168-177 doi: https://doi.org/10.14740/jem843

The role of polymorphisms of <I>PNPLA3</I>, <I>MBOAT7</I>, and <I>TM6SF2</I> in the development of non-alcoholic fatty liver disease in metabolic syndrome

Non-alcoholic fatty liver disease currently affects more than 30% of the population. Recent studies highlight the role of genetic polymorphisms in genes associated with fat catabolism and anabolism in the manifestation of this condition and its progression. The work analyzes foreign publications on the molecular and biochemical aspects of these polymorphisms, as well as works studying their effect on the state of the liver and markers of its pathology over the past 10 years. Thus, polymorphisms of the PNPLA3, MBOAT7, and TM6SF2, affecting the functionality of the proteins they express, lead to a change in the metabolism of fatty acids in the liver, which in turn leads to the development of NAFLD and its progression. Despite the fact that the contribution of the rs738409 polymorphism of the PNPLA3 gene is well described both in foreign and Russian articles, polymorphisms of the MBOAT7 and TM6SF2 genes and their effect on NAFLD, as well as the molecular biochemical mechanisms underlying it, have been studied much worse in foreign studies and are little mentioned in Russian ones. In addition, the issue of the severity of the influence of the above polymorphisms on populations of different ethnic and age groups requires additional research. This work attempts to systematize the available data on these issues.

Study of non-alcoholic fatty liver disease in metabolic syndrome

Background: Metabolic syndrome is a clustering of risk factors that increase an individual’s probability of developing atherosclerotic cardiovascular disease, type 2 diabetes mellitus and all cause mortality. Since primary NAFLD has strong association with metabolic syndrome as a whole and various components of metabolic syndrome, it is being debated whether NAFLD is a hepatic component of metabolic syndrome. Hence this study was done to study the prevalence of non-alcoholic fatty liver disease in healthy individuals and in patients with metabolic syndrome and to establish a relationship between NAFLD and Metabolic syndrome.Methods: A total of 122 patients - 61 with metabolic syndrome and 61 without metabolic syndrome fulfilling inclusion and exclusion criteria who presented to the Medicine outpatient Department of Ramaiah Medical College, Bangalore, between October 2014 and September 2016 were included in the study. Baseline variables, laboratory parameters, ultrasound abdomen findings were compared between the groups.Results: Mean age of the subjects in metabolic syndrome group and non-metabolic syndrome group were 52.4±15.4 and 50.7±15.4years respectively. Mean triceps skin fold thickness (in cms) for the subjects in metabolic syndrome group and non-metabolic syndrome group were 19.16±6.1 and 7.59±2.57 respectively (P <0.05). Prevalence of fatty liver on ultrasonography in metabolic syndrome and non-metabolic syndrome were 42.62 % and 21.31% respectively. Overall prevalence of NAFLD was 31.97 %.Conclusions: Overall prevalence of NAFLD from current study was 31.97%. The prevalence of NAFLD was significantly higher in persons with metabolic syndrome than persons without metabolic syndrome.

Association of tissue inhibitor of metalloproteinase 2 with non-alcoholic fatty liver disease in metabolic syndrome

The aim of this case–control study was to assess TIMP2 level in subjects with or without metabolic syndrome (MetS) and to associate levels with non-alcoholic fatty liver changes (NAFLD). Thirty-three MetS subjects and 55 controls were recruited. Anthropometric data, lipid and glucose profile, TIMP2 and liver ultrasound was performed. High TIMP2 was seen in MetS group (145.28 ± 23.11 pg/ml) versus controls (19.06 ± 1.19 pg/ml; p < .001). Serum cholesterol, triglyceride, LDL-c and glucose levels were significantly higher in MetS subjects (p < .05). MetS individuals (72.72%) showed positive fatty liver changes versus 14.5% controls. Elevated TIMP2 positively correlated with waist circumference, body fat, blood glucose and NAFLD. Furthermore, every unit rise in waist circumference and TIMP2 and a unit decrease in HDL were associated with higher odds of developing NAFLD (p < .05). There may be concurrent relationship between TIMP2 and NAFLD in MetS that requires further evaluation to improve risk assessment and early diagnosis of MetS.

Predictors of non-alcoholic fatty liver disease in metabolic syndrome

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

A Redox-resistant Sirtuin-1 Mutant Protects against Hepatic Metabolic and Oxidant Stress

Sirtuin-1 (SirT1), a member of the NAD(+)-dependent class III histone deacetylase family, is inactivated in vitro by oxidation of critical cysteine thiols. In a model of metabolic syndrome, SirT1 activation attenuated apoptosis of hepatocytes and improved liver function including lipid metabolism. We show in SirT1-overexpressing HepG2 cells that oxidants (nitrosocysteine and hydrogen peroxide) or metabolic stress (high palmitate and high glucose) inactivated SirT1 by reversible oxidative post-translational modifications (OPTMs) on three cysteines. Mutating these oxidation-sensitive cysteines to serine preserved SirT1 activity and abolished reversible OPTMs. Overexpressed mutant SirT1 maintained deacetylase activity and attenuated proapoptotic signaling, whereas overexpressed wild type SirT1 was less protective in metabolically or oxidant-stressed cells. To prove that OPTMs of SirT1 are glutathione (GSH) adducts, glutaredoxin-1 was overexpressed to remove this modification. Glutaredoxin-1 overexpression maintained endogenous SirT1 activity and prevented proapoptotic signaling in metabolically stressed HepG2 cells. The in vivo significance of oxidative inactivation of SirT1 was investigated in livers of high fat diet-fed C57/B6J mice. SirT1 deacetylase activity was decreased in the absence of changes in SirT1 expression and associated with a marked increase in OPTMs. These results indicate that glutathione adducts on specific SirT1 thiols may be responsible for dysfunctional SirT1 associated with liver disease in metabolic syndrome.

Effect of multifactorial treatment on non-alcoholic fatty liver disease in metabolic syndrome: a randomised study

ABSTRACTBackground: Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome (MetS). There is no established treatment for NAFLD.Aim: To evaluate a multifactorial intervention in the treatment of NAFLD.Methods: A prospective, open-label, randomised study in non-diabetic patients (n = 186) with MetS (follow-up: 54 weeks). All patients had both biochemical and ultrasonographic evidence of NAFLD at baseline. Other causes of liver disease were excluded. Patients received lifestyle advice and treatment for hypertension (mainly inhibitors of the renin–angiotensin system), impaired fasting glucose (metformin), obesity (orlistat) and dyslipidaemia [randomly allocated to atorvastatin 20 mg/day (n = 63) or micronised fenofibrate 200 mg/day (n = 62) or both drugs (n = 61)]. Liver ultrasonography was assessed at baseline and at the end of the study.Results: At the end of treatment, 67% of patients on atorvastatin, 42% on fenofibrate and 70% on combination treatment no longer had biochemical plus ultrasonographic evidence of NAFLD ( p < 0.05 vs. baseline for all comparisons). The percentage of patients who no longer had evidence of NAFLD was significantly higher ( p < 0.009) in the atorvastatin and combination groups compared with the fenofibrate group. This effect was independently related to drug treatment, as well as to reductions in high-sensitivity C-reactive protein, waist circumference, body weight, triglycerides, low-density lipoprotein-cholesterol, total cholesterol, systolic blood pressure and glucose. Four patients discontinued treatment because of adverse effects.Conclusions: Multifactorial intervention in MetS patients with both biochemical and ultrasonographic evidence of NAFLD offsets surrogate markers of NAFLD (i.e. elevated aminotransferase plus echogenic liver).

17 Prevalence of fatty liver disease in metabolic syndrome

17 Prevalence of fatty liver disease in metabolic syndrome