Abstract 19255: Double Knockout of Akt2 and AMPK Resists High Fat Diet-Induced Adiposity, Cardiac Dysfunction and Hepatic Steatosis
Akt and AMPK are two essential sometimes reciprocal signaling regulatory machineries governing energy homeostasis and insulin action. This study was designed to examine the high fat diet intake-induced stress responses in the absence of Akt2 and AMPK. Double knockout (DKO) model of Akt2 and AMPK was generated by crossing single knockout lines before placing DKO (and WT) mice on high fat (45% calorie from fat) or low fat (10% calorie from fat) diets for 5 months. Glucose metabolism, energy homeostasis, cardiac function, lipid accumulation and hepatic steatosis were examined. DKO mice were lean with normal cardiac and hepatic functions under normal diet intake. High fat diet intake resulted in impaired glucose tolerance, greater body weight gain and decreased ambulatory activity, oxygen consumption (VO2), respiratory exchange ratio (RER) and energy expenditure and compromised function of heart and liver in WT mice, all of which were significantly reconciled by DKO. DKO mice fed high fat diet exhibited significantly lower serum levels of insulin, triglycerides and cholesterol with preserved cardiac and liver functions compared with WT mice fed high fat. DEXA scanning revealed significantly higher fat mass and lower lean mass in WT mice fed high fat diet compared with DKO mice fed fat diet. Histopathological analysis of liver revealed decreased liver steatosis in DKO mice as evidenced by lower triglycerides, glycogen and lipid droplets density. In addition, DKO mice displayed less epididymal, inguinal and retroperitoneal fat accumulation compared with WT mice fed high fat diet. The white adipocyte size in DKO mice fed high fat diet was significantly less compared with fat diet fed WT mice. Similarly brown adipocytes were significantly smaller in DKO mice fed high fat diet compared with fat fed WT mice. Taken together, our findings suggest that double ablation of Akt2 and AMPK resists against fat diet-induced cardiac and hepatic anomalies possibly through preservation of energy homeostasis and lipid metabolism. These findings suggest a novel therapeutic avenue for the management of fat diet-induced adiposity, cardiac and liver dysfunction.
Author Disclosures: S. Wang: None. Y. Zhang: None. J. Ren: None.
- © 2016 by American Heart Association, Inc.