Polyunsaturated Fatty Acids Stimulate De novo Lipogenesis and Improve Glucose Homeostasis during Refeeding with High Fat Diet

Aims: The recovery of body weight after a period of caloric restriction is accompanied by an enhanced efficiency of fat deposition and hyperinsulinemia—which are exacerbated by isocaloric refeeding on a high fat diet rich in saturated and monounsaturated fatty acids (SFA-MUFA), and poor in polyunsaturated fatty acids (PUFA), and associated with a blunting of de novo lipogenesis in adipose tissue and liver. As high fat diets rich in PUFA have been shown to limit the excess fat deposition and improve glucose homeostasis, we investigated here the extent to which de novo lipogenesis in liver and adipose tissues (white and brown), as well as hepatic oxidative stress, are influenced by refeeding on diets rich in PUFA. Design: In rats calorically restricted for 14 days and refed for 14 days on isocaloric amounts of a high fat diet rich in lard (i.e., high SFA-MUFA) or in safflower and linseed oils (rich in PUFA), we investigated energy balance, body composition, glycemic profile, and the regulation of fatty acid synthase (rate-limiting enzyme of de novo lipogenesis) in liver, white and brown adipose tissue. We also evaluated oxidative stress in liver and skeletal muscle and markers of hepatic inflammation. Results: Rats refed the PUFA diet gained less lipids and more proteins compared to rats refed SFA-MUFA diet and showed lower amount of visceral and epididymal white adipose tissue, but increased depots of interscapular brown adipose tissue, with higher expression of the uncoupling protein 1. A significant increase in non-protein respiratory quotient and carbohydrate utilization was found in rats refed PUFA diet. Rats refed PUFA diet showed improved glucose homeostasis, as well as lower triglycerides and cholesterol levels. Fatty acid synthase activity was significantly higher in liver, white and brown adipose tissue, while lipid peroxidation and the degree of inflammation in the liver were significantly lower, in rats refed PUFA diet. Conclusions: When considering the composition of high fat diets for nutritional rehabilitation, the inclusion of PUFA could be useful for improving protein deposition and maintaining glucose homeostasis, while limiting lipid storage in adipose tissue and oxidative stress and inflammation in the liver.