High-fat diet from perilla oil induces insulin resistance despite lower serum lipids and increases hepatic fatty acid oxidation in rats

Background: The purpose of this study is to investigate the effects of a high-fat diet from perilla oil on serum lipids, hepatic lipid metabolism and insulin sensitivity. Methods: Male Sprague–Dawley (SD) rats were fed either a control (CT) diet or a diet high in perilla oil (HP). After 16 weeks of feeding, the serum lipids were measured, and the gene expressions involved in hepatic fatty acid oxidation and synthesis were determined. In addition, hepatic fat deposition was detected, and insulin sensitivity was evaluated by means of euglycemic-hyperinsulinemic clamp. Results: Compared with the rats in the CT group, the HP-feeding significantly decreased the levels of triglyceride (TG), total cholesterol (TCH) and HDL-cholesterol (HDL-c). HP-feeding did not change the levels of LDL-cholesterol (LDL-c), free fatty acid (FFA), intrahepatic lipids or body weight. Moreover, the HP-feeding dramatically increased the mRNA expressions of fatty acid oxidation markers (PPAR-alpha, CPT1A) and fatty acid synthesis markers (SREBP-1, FASN and ACC) in the liver. The HP-feeding induced increased protein levels of CPT1A, while reducing the protein levels of FASN and ACC in the liver. However, the glucose infusion rate significantly increased in the HP group compared with the CT group. Conclusions: Our data show that, in rats, excessive perilla oil intake may significantly lower serum lipids, strengthen hepatic fatty acid oxidation, and inhibit hepatic fatty acid synthesis, but at the same time may also lead to insulin resistance.