Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease that can progress from simple hepatic steatosis to nonalcoholic steatohepatitis (NASH), and even further to liver cirrhosis or liver cancer. Overconsumption of high fat and/or carbohydrate are among the most common lifestyle factors that drive the development and progression of NAFLD. This review evaluates recent reports on the involvement of autophagy and endoplasmic reticulum (ER) stress in the pathogenesis of NAFLD. Here, we reveal a mechanism of an intrinsically linked axis of impaired autophagy and unresolved ER stress that mediates the development and progression of NAFLD resulting from the overconsumption of high fat and/or carbohydrate.

Albiflorin (AF) is a small molecule (MW 481) isolated from Paeoniae radix, a plant used as a remedy for various conditions with pathogenesis shared by metabolic diseases. Reported here is our characterization of its therapeutic profiles in three mouse models with distinctive pathological features of metabolic syndrome (MetS). Our results firstly showed that AF alleviated high fat (HF) induced obesity and associated glucose intolerance, suggesting its therapeutic efficacy for MetS. In the type 2 diabetes (T2D) model induced by a combination of HF and low doses of streptozotocin, AF lowered hyperglycaemia and improved insulin-stimulated glucose disposal. In the non-alcoholic steatohepatitis-like model resulting from a HF and high cholesterol (HF-HC) diet, AF reversed the increased liver triglyceride and cholesterol, plasma aspartate aminotransferase, and liver TNFα mRNA levels. Consistent with its effect in promoting glucose disposal in HF-fed mice, AF stimulated glucose uptake and GLUT4 translocation to the plasma membrane in L6 myotubes. However, these effects were unlikely to be associated with activation of insulin, AMPK, ER, or cellular stress signalling cascades. Further studies revealed that AF increased the whole-body energy expenditure and physical activity. Taken together, our findings indicate that AF exerts a therapeutic potential for MetS and related diseases possibly by promoting physical activity associated whole-body energy expenditure and glucose uptake in muscle. These effects are possibly mediated by a new mechanism distinct from other therapeutics derived from Chinese medicine.

Diets(饮食) rich in fat are a major(主要) cause(原因) of metabolic disease(疾病), and nutritional(营养) food has been widely(广泛) used(使用) to counteract the metabolic disorders such(这样) as obesity(肥胖) and fatty(脂肪) liver(肝). The present study investigated the effects of oleuropein-enriched extract(提取物) from Jasminum grandiflorum L. flowers (OLE-JGF) in high-fat diet(饮食) (HFD)-fed mice and oleic acid(酸) (OA)-treated AML-12 cells. Treatment(治疗) of HFD-fed mice with 0.6% OLE-JGF for 8 weeks significantly reduced body and liver(肝) weights, as well as attenuating lipid dysmetabolism and hepatic steatosis. OLE-JGF administration(政府当局) prominently suppressed the mRNA expressions(表达) of monocyte chemoattractant protein(蛋白)-1 (MCP-1) and cluster of differentiation 68 (CD68), and it also downregulated acetyl-CoA carboxylase (ACC) and fatty(脂肪) acid(酸) synthase (FAS) as well as sterol-regulatory-element(元素)-binding protein(蛋白) (SREBP-1c) in the liver(肝). Meanwhile, mitochondrial DNA and uncoupling protein(蛋白) 2 (UCP2) were upregulated along with the increased expression(表达) of mitochondrial biogenic promoters including liver(肝) kinase B1 (LKB1), peroxisome proliferator–activated receptor-γ coactivator-1α (PGC-1α), nuclear(核) factor(因子)-erythroid-derived 2-like 2 (Nrf2), and mitochondrial transcription factor(因子) A (Tfam), but did not change AMP-activated protein(蛋白) kinase (AMPK) in liver(肝). The lipid droplets were decreased significantly after treatment(治疗) with 80 μM oleuropein for 24 h in OA-induced AML-12 cells. Furthermore, oleuropein significantly inhibited ACC mRNA expression(表达) and upregulated LKB1, PGC-1α, and Tfam mRNA levels, as well as increasing the binding level of LKB1 to PGC-1α promoter in OA-induced cells. These findings indicate(表明) that OLE-JGF reduces hepatic lipid deposition in HFD-fed mice, as well as the fact that OA-induced liver(肝) cells may be partly(部分) attributed to upregulation of the LKB1-PGC-1α axis, which mediates hepatic lipogenesis and mitochondrial biogenesis. Our study provides a scientific(科学) basis(基础) for the benefits and potential(潜在) use(使用) of the J. grandiflorum flower as a food supplement(补充) for the prevention(预防) and treatment(治疗) of metabolic disease(疾病).