Aliskiren effect on non-alcoholic steatohepatitis in metabolic syndrome

Abstract

BackgroundNon-alcoholic steatohepatitis (NASH) is highly associated with metabolic syndrome, a major cause of morbidity in the globalized society. The renin–angiotensin system (RAS) influences hepatic fatty acid metabolism, inflammation and fibrosis. Thus, in the present study, we aimed to evaluate the effect of aliskiren, a direct renin inhibitor, on metabolic syndrome-related NASH.MethodsC57BL/6 male mice (n = 45) were divided into three groups: controls; animals inoculated with streptozotocin (STZ) (40 mg/kg/day) for 5 days and fed with high fat diet (HFD) for 8 weeks; and animals inoculated with STZ for 5 days, fed with HFD for 8 weeks and treated with aliskiren (100 mg/kg/day) for the final 2 weeks. Glycemic and insulin levels, hepatic lipid profile, histological parameters and inflammatory protein expression were analyzed.ResultsAliskiren normalized plasma glucose and insulin levels, reduced cholesterol, triglycerides and total fat accumulation in liver and diminished hepatic injury, steatosis and fibrosis. These results could be explained by the ability of aliskiren to block angiotensin-II, lowering oxidative stress and inflammation in liver. Also, it exhibited a beneficial effect in increasing insulin sensitivity.ConclusionThese findings support the use of aliskiren in the treatment of metabolic syndrome underlying conditions. However, clinical studies are indispensable to test its effectiveness in the treatment of patients with metabolic syndrome.

A high‐fat diet reverses metabolic disorders and premature aging by modulating insulin and IGF1 signaling in SIRT6 knockout mice

“…The SIRT6 deficiency induced overactivation of IR and IGF1R in the heart tissue even without any change of blood insulin or glucose levels, which suggests that phosphorylation of IR and IGF1R is regulated by SIRT6 but not secondary effect of blood glucose or insulin (Sundaresan et al, ). It has been demonstrated that a high‐fat diet can decrease p‐IR levels and inhibit the activation of AKT, and also decrease glucose uptake and promote insulin resistance (Nguyen et al, ; Ramalho et al, ; Singh et al, ; Sodhi et al, ). Although insulin resistance is widely accepted as a risk factor of diabetes, it is a necessary response to evolutionary pressure when the main challenges to survival are not obesity and diabetes, but acute trauma and prolonged fasting (Soeters & Soeters, ).…”

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