Protective effect of alpha-tocopherol on lipogenesis and oxysterol production in hypercholesterolemia-induced nonalcoholic steatohepatitis.

Despite limited number of studies, oxysterols are known to contribute to the progression of nonalcoholic steatohepatitis (NASH) by affecting lipid/cholesterol metabolism and elevating proinflammatory and profibrotic processes. Accordingly, we used a high cholesterol-mediated in vivo NASH model and aimed to determine alterations in fatty acid content and oxysterol levels together with their effects on cholesterol/lipid metabolism during the progression of the disease. We further investigated the beneficial role of α-tocopherol.

Impact of Seipin in cholesterol mediated lipid droplet maturation; status of endoplasmic reticulum stress and lipophagy.

The global prevalence of nonalcoholic fatty liver disease (NAFLD) defined by the increased number of lipid droplets (LDs) in hepatocytes, have risen continuously in parallel with the obesity. LDs and related proteins are known to affect cellular metabolism and signaling. Seipin, one of the most important LD-related proteins, plays a critical role in LD biogenesis.

Cholesterol accumulation in hepatocytes mediates IRE1/p38 branch of endoplasmic reticulum stress to promote nonalcoholic steatohepatitis.

Non-alcoholic fatty liver disease (NAFLD), based on the elevating obesity incidence, is one of the major health issue worldwide. Transition from NAFLD to non-alcoholic steatohepatitis (NASH) is driven by increased apoptosis and is relevant to higher morbidity rates. In regard to limited understanding on cholesterol mediated hepatocyte alterations in NALFD/NASH transition, we investigated endoplasmic reticulum (ER) stress and related apoptosis.

Endoplasmic Reticulum Stress and miRNA Impairment in Aging and Age-Related Diseases.

Aging is a physiological process defined by decreased cellular and tissue functions. Reduced capacity of protein degradation is one of the important hallmarks of aging that may lead to misfolded protein accumulation and progressive loss of function in organ systems. Recognition of unfolded/misfolded protein aggregates endoplasmic reticulum (ER) stress sensors activates an adaptive mechanism, the unfolded protein response (UPR).

Deficiency of SREBP1c modulates autophagy mediated lipid droplet catabolism during oleic acid induced steatosis.

Objective: Increased fatty acid and triglyceride synthesis in liver, majorly modulated by Sterol Regulator Elementing Binding Protein 1c (SREBP1c), is one of the main features of non-alcoholic fatty liver disease (NAFLD). In the present study, we aimed to identify the relation between SREBP1c and autophagy mediated lipid droplet (LD) catabolism in oleic acid (OA) induced lipid accumulation.

Methods: Increased LD formation and SREBP1c induction were identified in hepatocytes (AML12 cells) following the OA administration.

High cholesterol diet activates ER stress mediated apoptosis in testes tissue: Role of α-tocopherol.

The seminiferous tubules where spermatogenesis occurs are enveloped and protected by the Sertoli cells to support germ cells undergoing meiosis to produce haploid gametes. Clearly, induction of apoptosis in seminiferous tubules leads to abnormalities in spermatogenesis and male infertility. Studies demonstrated that increased hyperlipidemia impairs male infertility and spermatogenesis by enhancing seminiferous tubules apoptosis.

alpha-Tocopherol supplementation reduces inflammation and apoptosis in high cholesterol mediated nonalcoholic steatohepatitis.

Inflammation and apoptosis signaling are crucial steps in the progression from nonalcoholic fatty liver disease (NAFLD) to nonalcoholic steatohepatitis (NASH). Alpha-tocopherol, the most active form of vitamin E, is an important modulator of signaling mechanisms, but its involvement to cholesterol-induced NASH pathogenesis remains poorly defined. Herein we have reported a novel effect of α-tocopherol in the transition from hepatic steatosis to NASH.