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 20 weeks, then the HFD + FF rats were administered FF (30 mg/kg once daily via gavage) for another 8 weeks. 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.
Eight weeks of FF treatment attenuated HFD-induced IR by decreased tribbles 3 (TRB3) expression, ER stress and inflammation in skeletal muscle. FA pretreatment markedly inverted the PA-induced expression of TLR4 and downstream inflammatory genes, activated ER stress, improved β-oxidation and insulin signaling in differentiated myotube cells.
FF treatment significantly improved HFD-induced IR in skeletal muscle and PA-induced IR in myotube cells, which may be related to reduced ER stress-induced inflammation.