Effects of acute and longer-term moderate dietary restriction on gut motility, hormone, appetite and energy intake responses to duodenal lipid in lean and obese males

Abstract

and insulin action. Plin5−/− mice developed normally with lean and fat masses the same as wild-type mice following low fat (5% energy from fat) and high fat diet (59% energy from fat). Indirect calorimetry revealed an increase in the respiratory exchange ratio in Plin5−/− mice fed a low fat and high fat diet, demonstrating a decrease in whole-body fatty acid oxidation and a reciprocal increase in carbohydrate oxidation. Studies in myotubes isolated from the skeletal muscle of Plin5−/− mice showed that PLIN5 deletion increases the oxidation of fatty acids derived from triglyceride under basal and -adrenergic stimulated conditions. These changes occurred independently of alterations in mitochondrial function or oxidative capacity and support the notion that PLIN5 suppresses triglyceride breakdown. These changes in lipid metabolism prompted us to investigate the effect PLIN5 on insulin action. Plin5−/− mice have improved glucose tolerance (2mg/kg glucose i.p) on LF and HF diet, but Plin5−/− mice on LFD (assessed with euglycemic-hyperinsulmaemic) had impaired whole-body insulin action. This was not associated with any changes in ceramide or diacylglycerol content. These results suggest that PLIN5 exerts mild effects on lipid metabolism in skeletal muscle and that PLIN5 deletion results in tissue-specific effects on insulin action. Further studies using tissuespecific Plin5−/− will help to determine the biology underpinning these differences.