Fenofibrate improves high-fat diet-induced and palmitate-induced endoplasmic reticulum stress and inflammation in skeletal muscle

Publication date: Available online 11 June 2016 Source:Life Sciences Author(s): Fang Dai, Tian Jiang, Ying-ying Bao, Guan-jun Chen, Li Chen, Qiu Zhang, Yun-xia Lu Aims Fenofibrate (FF) is commonly used clinically as a lipid-lowering drug, but whether it participates in endoplasmic reticulum (ER) stress and decreases inflammation in skeletal muscle is still unknown. The aim of this study is to determine whether FF treatment reduces insulin resistance (IR) by alleviating ER stress and downstream inflammation in skeletal muscle tissues and cells. Main methods Female SD rats were randomly divided into groups receiving the standard chow diet (SCD), a high-fat diet (HFD), or HFD plus FF (HFD+FF). The rats in the latter two groups were subjected to a standard HFD for 20weeks, then the HFD+FF rats were administered FF (30mg/kg once daily via gavage) for another 8weeks. Whole-body IR, expression of peroxisome proliferator-activated receptor α (PPARα), ER stress-related genes, and inflammatory genes in the soleus muscle were assessed. The differentiated C2C12 myotubes were treated with palmitic acid or pretreated with fenofibric acid or 4-phenylbutyric acid (4-PBA), etomoxir, and the expression of ER stress, beta-oxidation-related genes, inflammatory genes, Toll-like receptor 4 (TLR4), and insulin-signaling-related molecules were determined. Key findings Eight weeks of FF treatment attenuated HFD-induced IR by decreased tribbles 3 (TRB3) expression, ER stress an...
Source: Life Sciences - Category: Biology Source Type: research