The Role of Hepatic AMPK in Metabolic Adaptation under High-Protein Diet

WOS:000361722702131International audienceHigh protein diets are recognized to reduce food intake and body fat gain. As hepatic AMPK is involved in the transduction of both amino acid signals and energy sensing, we tested the hypothesis that high protein diets can affect metabolism via this pathway. We, therefore, compared the metabolic responses of wild type and liver-specific AMPK-KO mice to a low, normal and high protein diet. 24 wild–type (WT) and 24 liver specific AMPK-KO (KO) C57BL/6 mice were respectively split in 3 groups (N=8/group) fed during 3 weeks on a low (5%, LP) normal (14%, NP) and high (55%, HP) protein diet. Food intake was measured, body composition was followed by Dual energy X-ray absorptiometry and changes in the rates of glucose and lipid oxidation were assessed by indirect calorimetry following ingestion of a calibrated test meal. No difference in fat mass gain or food intake was observed between WT and KO mice under LP and HP diet but KO mice tended to eat more and to gain less fat mass when fed the NP diet. Results from indirect calorimetry showed that in KO mice fed the HP and LP diets the increase in glucose oxidation and decrease in lipid oxidation induced by ingestion of the test meal were of lower amplitude than in WT mice. Under NP diet, the responses were of the same amplitude but occurred with a delay of ~2 hours. This study suggests that consequences of the knockout of liver AMPK on energy homeostasis depend on the protein content of the diet; we observed no significant effect under LP and HP despite significant alterations of post-meal glucose and lipid metabolism. In contrast, we observed reduced energy efficiency under NP diet associated with delayed changes in fuel oxidations after meal ingestion