Influence of Genistein and Exercise on Lipid Metabolism in High Fat‐High Sugar Fed Mice

Abstract

Intake of diets high in saturated fat with sugar have been associated with chronic diseases including type 2 diabetes and Alzheimer's disease (AD). This study varied diet and exercise and assessed the changes in adipose metabolism by measuring serum markers, hepatosteatosis, and skeletal muscle lipid metabolism. Male and female 5–6 week old C57BL/6J mice were randomly assigned one of the following groups for 12 weeks (n=8–10/group): lean control (Ln), high fat diet, HFD (60% of calories from fat), and high sucrose/fructose (42 g combined/L drinking water) (HFHS), HFHS with genistein (Gen), HFHS with exercise (Ex), or HFHS with genistein and exercise (Gen‐Ex). Exercise consisted of 150 min/week forced treadmill running. Genistein dose was 600 mg genistein/kg HFD. We hypothesize that Ex and Gen will improve deficits in lipid metabolism associated with diabetes and obesity. Males and females had significant weight increase in HFHS groups compared to Ln groups (40.8% and 27.5% respectively, P<0.05). In males, body weight was significantly lower in Ex (8.9%), Gen (19.2%) and Gen‐Ex mice (32.6%, P<0.05) compared to HFHS controls. In females, body weight was significantly lower in the Gen‐Ex (20.7%, P<0.05) compared to HFHS controls. Weight loss was not attributed to reduced food intake, nor correlated to comparable changes in serum triglyceride. Male liver weight/body weight was increased in HFHS (31.8%, P<0.05) versus Ln, and subsequently reduced by Ex (23.5%), Gen (39%) and Gen‐Ex (52%, P<0.05) compared to HFHS controls. Female liver/body weight was comparable between groups. Glucose tolerance tests (GTT) in subgroups of mice (n=3–5/group) showed rescue of serum glucose in Gen‐Ex males (not females), which reflected concomitant changes in serum insulin. Protein expression of the skeletal muscle lipid metabolism marker, carnitine palmitoyltransferase 1b (CPT1b) was greater (80.5%, n=5/group, P<0.05) in males fed HFHS compared to Ln controls, with no differences in treatment interventions. We aim to provide mechanistic evidence for sex‐dependent effects and to demonstrate an association between genistein‐ and exercise‐mediated improvements in diet induced diabetic‐obesity. Current studies continue to evaluate other metabolic markers. Data currently suggests significant weight changes are not correlated with concomitant changes in skeletal muscle lipid metabolism markers.Support or Funding InformationLayla Al‐Nakkash, and Tom Broderick were supported by Midwestern‐Arizona Alzheimer's Consortium and Midwestern Intramural funds. Amy Fisher and Chaheyla St Aubin were supported by the Department of Biomedical Sciences.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.