PMC:4277126 / 71348-75149
Annnotations
{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/4277126","sourcedb":"PMC","sourceid":"4277126","source_url":"http://www.ncbi.nlm.nih.gov/pmc/4277126","text":"Nonalcoholic fatty liver disease\nNonalcoholic fatty liver disease (NAFLD) is a chronic metabolic liver disease that histologically resembles the alcohol-induced hepatic injury, but is not caused by alcohol abuse.92,93 It is a spectrum of disease ranging from simple steatosis, to non-alcoholic steatohepatitis, through to advanced fibrosis and cirrhosis. NAFLD is associated with other medical conditions such as metabolic syndrome, obesity, cardiovascular disease, and diabetes.92,93 Mechanisms involved in the pathogenesis are associated with diet and lifestyle, influx of free fatty acids to the liver from adipose tissue due to insulin resistance, hepatic oxidative stress, cytokines production, reduced very low-density lipoprotein secretion, and intestinal microbiome.94 In Western countries, NAFLD affects 20%–40% of the adult populations. Weight loss through improved diet and increased physical activity has been the cornerstone therapy of NAFLD, but no drugs are approved for use in NAFLD.93,95\nIn a study conducted by Xiao et al96,97 female rats were fed with a high-fat diet (HD) to induce nonalcoholic steatohepatitis, with or without an oral 1 mg/kg LBP feeding, daily for 8 weeks. LBP-treated rats showed improved histology and free fatty acid levels, rebalance of lipid metabolism, reduction in profibrogenic factors through the transforming growth factor (TGF)-β/small mothers against decapentaplegic pathway, improved oxidative stress through cytochrome P450 2E1-dependent pathway, reduction in hepatic proinflammatory mediators and chemokine production, and amelioration of hepatic apoptosis through the p53-dependent intrinsic and extrinsic pathways.96\nA mouse study by Li et al98 investigated whether LBPs prevented fatty liver through activation of adenosine monophosphate-activated protein kinase (AMPK) and suppression of sterol regulatory element-binding protein-1c (SREBP-1c).98 Male C57BL/6J mice were fed a low-fat diet, HD, or 100 mg/kg LBP-treatment diet for 24 weeks. The results showed that LBPs improved body compositions and lipid metabolic profiles in high-fat diet-fed mice. Oil Red O staining showed that LBPs significantly reduced hepatic intracellular triacylglycerol accumulation. Hepatic genes expression profiles demonstrated that LBPs activated the phosphorylation of AMPK, suppressed nuclear expression of SREBP-1c, and decreased protein and mRNA expression of lipogenic genes.98\nLin et al99 investigated whether AMPKα2 is essential for the protective effects of wolfberries on mitochondrial dysfunction and subsequent hepatic steatosis in mice. Six-week-old male AMPKα2 knockout mice and genetic background C57BL/6J mice were fed a control, HD (45% [kilocalorie] fat), and/or HD with 5% (kilocalorie) wolfberry diets for 18 weeks. HD feeding for 18 weeks lowered hepatic lutein and zeaxanthin contents, inhibited protein expression of β,β-carotene 9′,10′-oxygenase 2 and heat shock protein 60 (HSP60) in mitochondria, increased reactive oxygen species level, suppressed mitophagy and mitochondrial biogenesis as determined by accumulation of p62, inhibited phosphorylation of Unc-51-like kinase 1 on Ser555, and decreased expression of peroxisome proliferator-activated receptor-γ coactivator 1α, resulting in hepatic steatosis in AMPKα2 knockout and C57BL/6J mice.99 Dietary wolfberry elevated the xanthophyll concentrations and enhanced expression of β,β-carotene 9′,10′-oxygenase 2 and HSP60, attenuated mitochondrial oxidative stress, activated AMPKα2, potentiated mitophagy and mitochondrial biogenesis, and enhanced lipid oxidation and secretion in the liver of C57BL/6J mice.99 Dietary wolfberry selectively activated AMPKα2, enhanced mitochondrial biogenesis, and potentiated mitophagy, leading to the prevention of hepatic steatosis in obese 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