Oxidative stress and inflammation contribute to hypertriglyceridemia‐induced nonalcoholic fatty liver disease (NAFLD). Cholesterol‐enriched diets increase the risk of NAFLD. Lycium ruthenium Murr. (LRM) contains water‐soluble antioxidant proanthocyanidins. Whether Lycium ruthenium Murr. improves NAFLD remains elusive. In this study, we established a model of NAFLD‐induced by cholesterol‐enriched high‐fat diet (western diet) in ApoE−/− mice; oxidative stress and inflammation were examined and intervened by supplement of Lycium ruthenium Murr. (LRM) extracts. LRM supplement did not influence body weight gain, food intake, and lipotoxicity of mice. LRM supplement significantly alleviated triglyceride accumulation in liver, with reduced inflammation, elevated GSH‐Px activity, and reduced MDA levels. The expression of fatty acids oxidative gene Scd1 was significantly increased, and fatty acids synthesis‐related gene Pparγ was dramatically downregulated on mRNA level in liver of mice with LRM supplement. These data demonstrated that LRM supplement decreased ROS production and inflammation, increased fatty acids oxidation, and reduced fatty acids synthesis in liver, leading to ameliorate the development of NAFLD induced by high western diet. Thus, oxidative stress and inflammation also are involved in the pathogenesis of western diet‐induced NAFLD, which is independent of obesity.

Objective Elevation of energy expenditure through an increase of brown adipose tissue (BAT) thermogenesis is regarded as one of the most promising ways to prevent obesity development. The preoptic area (POA) of the hypothalamus is a critical area for control of BAT thermogenesis. However, the intracellular signaling cascades in the POA for regulation of BAT thermogenesis are poorly understood. Methods Phosphorylation proteomics (phosphoproteomics) and bioinformatics approaches were used to disclose numerous hypothalamic signaling pathways involved in the regulation of BAT thermogenesis. Conditional manipulation of the p38α gene in mouse POA was performed by stereotaxic injection of adeno‐associated virus 9 vector to explore the role of p38α in BAT thermogenesis. Results Multiple hypothalamic signaling pathways were triggered by cold exposure, especially the mitogen‐activated protein kinase (MAPK) signaling pathway. The p38α activation, but not extracellular signal‐regulated kinase 1/2 (ERK1/2) and c‐Jun NH2‐terminal kinase (JNK), in the hypothalamus was significantly decreased during cold exposure. p38α deficiency in the POA dramatically elevated energy expenditure owing to a marked increase in BAT thermogenesis, resulting in significantly decreased body weight gain and fat mass. Overexpression of p38α in the POA led to a dramatic increase in weight gain. Conclusions These results demonstrate that p38α in the POA exacerbates obesity development, at least in part owing to a decrease in BAT thermogenesis.

Background Patients with estrogen receptor negative (ER−) breast cancer have poor prognosis due to high rates of metastasis. However, there is no effective treatment and drugs for ER− breast cancer metastasis. Our purpose of this study was to evaluate the effect of lotus leaf alcohol extract (LAE) on the cell migration and metastasis of ER− breast cancer. Methods The anti-migratory effect of LAE were analyzed in ER− breast cancer cells including SK-BR-3, MDA-MB-231 and HCC1806 cell lines. Cell viability assay, wound-healing assay, RNA-sequence analysis and immunoblotting assay were used to evaluate the cytotoxicity and anti-migratory effect of LAE. To further investigate the inhibitory effect of LAE on metastasis in vivo, subcutaneous xenograft and intravenous injection nude mice models were established. Lung and liver tissues were analyzed by the hematoxylin and eosin staining and immunoblotting assay. Results We found that lotus LAE, not nuciferine, inhibited cell migration significantly in SK-BR-3, MDA-MB-231 and HCC1806 breast cancer cells, and did not affect viability of breast cancer cells. The anti-migratory effect of LAE was dependent on TGF-β1 signaling, while independent of Wnt signaling and autophagy influx. Intracellular H2O2 was involved in the TGF-β1-related inhibition of cell migration. LAE inhibited significantly the breast cancer cells metastasis in mice models. RNA-sequence analysis showed that extracellular matrix signaling pathways are associated with LAE-suppressed cell migration. Conclusions Our findings demonstrated that lotus leaf alcohol extract inhibits the cell migration and metastasis of ER− breast cancer, at least in part, via TGF-β1/Erk1/2 and TGF-β1/SMAD3 signaling pathways, which provides a potential therapeutic strategy for ER− breast cancer.