scholarly journals Adipokines and melanocortins in the hepatic manifestation of metabolic syndrome: nonalcoholic fatty liver disease

2018 ◽  
Author(s):  
Mohammed H Jarrar

Metabolic syndrome is associated with nonalcoholic fatty liver disease and its moreaggressive form, nonalcoholic steatohepatitis. Adipokines produced by white adipose tissue possess broad physiological activity and play an important autocrine role in obesity-associated complications, including metabolic syndrome, nonalcoholic fatty liverdisease and cardiovascular disease. Various adipokines may have beneficial or harmfuleffects. Other tissues, particularly stomach and intestine, produce active molecules thatcan influence the function of adipocytes and, possibly, the levels of adipokine secretion. Insome cases, the production sites of these molecules remain unknown. The review focuses on our current understanding of the disease-related effects of the adipokines and the melanocortins on various peripheral tissues, and discusses some of their potentialinteractions with each other. Potential therapeutic applications are also considered.

2005 ◽  
Vol 152 (1) ◽  
pp. 113-118 ◽  
Author(s):  
Claudio Pagano ◽  
Giorgio Soardo ◽  
Walter Esposito ◽  
Francesco Fallo ◽  
Lorenza Basan ◽  
...  

Objectives: Nonalcoholic fatty liver disease (NAFLD) is a major cause of liver-related morbidity and is frequently associated with obesity and metabolic syndrome. The recently discovered hormone adiponectin is produced by adipose tissue, and low plasma adiponectin is considered a key factor in the development of the insulin resistance underlying metabolic syndrome. Animal studies suggest that adiponectin may protect against non-alcoholic steatohepatitis, but direct evidence in humans is lacking. We therefore conducted this study to assess the relationship between plasma adiponectin and nonalcoholic fatty liver disease to explore its role in the pathogenesis of this disease. Design and methods: We measured plasma adiponectin and anthropometric, biochemical, hormonal and metabolic correlates in a group of 17 NAFLD patients with diagnosis confirmed by biopsy, and 20 controls with comparable age, body-mass index and sex. Furthermore we compared plasma adiponectin in patients with simple steatosis and steatohepatitis. Results: Plasma adiponectin was significantly lower in NAFLD patients than controls (5.93±0.45 vs 15.67±1.60 ng/ml). Moreover, NAFLD patients were significantly more insulin resistant while having similar serum leptin. Adiponectin was similar in simple steatosis and in steatohepatitis (6.16±0.78 vs 5.69±0.49 ng/ml). An inverse correlation was observed between adiponectin and homeostatic model assessment (HOMA) of insulin resistance (P = 0.008), while adiponectin did not correlate with serum transaminases and lipid values. Conclusions: These data support a role for low circulating adiponectin in the pathogenesis of NAFLD and confirm the strict association between reduced adiponectin production by adipose tissue, NAFLD and insulin resistance.


2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Hongyun Lu ◽  
Hong Liu ◽  
Fang Hu ◽  
Lingling Zou ◽  
Shunkui Luo ◽  
...  

Nonalcoholic fatty liver disease (NAFLD) is closely correlated with insulin resistance and several metabolic syndrome features, but whether it could increase the risk of cardiovascular disease remains undefined. To assess the association between NAFLD and the risk of cardiovascular outcomes, we systematically searched the MEDLINE, Embase, and the Cochrane Library database (1947 to October 2012) by using Medical Subject Heading search terms and a standardized protocol. Randomized controlled trials, case-control, and prospective studies carried out in human adults, in which the unadjusted and multivariate adjusted odds ratios with corresponding 95% confidence interval (CI) for cardiovascular disease with NAFLD were reported. The search yielded 4 cross-sectional studies and 2 prospective cohort studies including 7,042 participants. The pooled effects estimate showed that NAFLD was a predictor of cardiovascular disease (odds ratio 1.88, 95% CI, 1.68 to 2.01; ). The random effects summary estimate indicated that NAFLD retained a significant association with cardiovascular outcomes independent of conventional risk factors after adjustment for established cardiovascular risk factors (odds ratio 1.50, 95% CI, 1.21 to 1.87; ). These results indicate that NAFLD is a strong independent predictor of cardiovascular disease and may play a central role in the cardiovascular risk of metabolic syndrome.


2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Mohamed H. Ahmed ◽  
Salma Barakat ◽  
Ahmed O. Almobarak

Nonalcoholic fatty liver disease (NAFLD) is prevalent in people with the metabolic syndrome and type 2 diabetes and is present in up to one-third of the general population. Evidence is now accumulating that NAFLD is associated with obesity and diabetes and may serve as a predictor of cardiovascular disease (CVD). The possible mechanisms linking NAFLD and CVD include inflammation and oxidative stress, hyperlipidaemia, insulin resistance, and direct impact of NAFLD on coronary arteries and left ventricular dysfunction. In addition, several studies suggest that NAFLD is associated with high risk of CVD and atherosclerosis such as carotid artery wall thickness and lower endothelial flow-mediated vasodilation independently of classical risk factors and components of the metabolic syndrome. It is not yet clear how treatment of NAFLD will modulate the risk of CVD. Furthermore, studies are urgently needed to establish (i) the pathophysiology of CVD with NAFLD and (ii) the benefit of early diagnosis and treatment of CVD in patients with NAFLD. In the absence of biochemical markers, it is crucial that screening and surveillance strategies are adopted in clinical practice in the growing number of patients with NAFLD and at risk of developing CVD. Importantly, the current evidence suggest that statins are safe and effective treatment for CVD in individuals with NAFLD.


2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Kei Nakajima

Nonalcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are multidisciplinary liver diseases that often accompany type 2 diabetes or metabolic syndrome, which are characterized by insulin resistance. Therefore, effective treatment of type 2 diabetes and metabolic syndrome should target not only the cardiometabolic abnormalities, but also the associated liver disorders. In the last decade, it has been shown that metformin, thiazolidinediones, vitamin E, ezetimibe, n-3 polyunsaturated fatty acids, renin-angiotensin system (RAS) blockers, and antiobesity drugs may improve hepatic pathophysiological disorders as well as clinical parameters. Accordingly, insulin sensitizers, antioxidative agents, Niemann-Pick C1-like 1 (NPC1L1) inhibitors, RAS blockers, and drugs that target the central nervous system may represent candidate pharmacotherapies for NAFLD and possibly NASH. However, the efficacy, safety, and tolerability of long-term treatment (potentially for many years) with these drugs have not been fully established. Furthermore, clinical trials have not comprehensively examined the efficacy of lipid-lowering drugs (i.e., statins, fibrates, and NPC1L1 inhibitors) for the treatment of NAFLD. Although clinical evidence for RAS blockers and incretin-based agents (GLP-1 analogs and dipeptidyl peptidase-4 inhibitors) is also lacking, these agents are promising in terms of their insulin-sensitizing and anti-inflammatory effects without causing weight gain.


2017 ◽  
Vol 37 (9) ◽  
pp. 1389-1396 ◽  
Author(s):  
Salvatore Petta ◽  
Mohammed Eslam ◽  
Luca Valenti ◽  
Elisabetta Bugianesi ◽  
Marco Barbara ◽  
...  

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