GLP‐1 analogue ameliorates hepatic steatosis and cardiac hypertrophy in mice fed transfat and high fructose corn syrup diet

Abstract

Obesity and insulin resistance (IR) cause a clustering of metabolic abnormalities including non-alcoholic fatty liver disease (NAFLD), dyslipidemia, hypertension and elevated plasma triglycerides. Western diets (WD) containing trans-fat (TF) and high fructose corn syrup (HFCS) have been shown to increase IR, fat mass and liver lipid accumulation. The Aim of the present study was to determine if liraglutide (LG), a glucagon-like peptide 1 (GLP-1) long-acting analogue could reverse the effects of a WD in mice including reduction in hepatic IR, steatosis and improved cardiac function. Male C57BL6 mice were fed ad libitum either standard chow or a high fat diet containing TF and HFCS for 8 wk, followed by 4 wk of concomitant daily LG injections. After LG injections, within the WD group, LG treatment significantly improved fasting serum glucose levels as compared with saline treated mice (122.2 mg/dL ± 6.17 vs. 166 mg/dL ± 50.73, p<.0001), reduced body weight (29.30 g ±.692 vs. 33.08 g ±4.54, p<.005), reduced liver weight (1.067 g ±.083 vs. 1.217 g ±.108, p<.05) heart weight (.006845 g/cm ± .000302 vs. .00755 g/cm ± .000612). LG liver and heart tissue had significantly higher levels of fatty acid binding protein and microsomal triglyceride transfer protein. Conclusion LG reduces the effects of a WD by improving insulin sensitivity and by reducing lipid accumulation in liver and heart through fatty acid uptake and transport. Grant Funding Source: R01 DK 075397