Date of Graduation

8-2016

Document Type

Thesis

Degree Name

Master of Science in Cell & Molecular Biology (MS)

Degree Level

Graduate

Department

Biological Sciences

Advisor

Jamie I. Baum

Committee Member

Tyrone Washington

Second Committee Member

Sun-Ok Lee

Third Committee Member

Walter Bottje

Fourth Committee Member

Jeffery Wolchok

Keywords

Biological sciences; Health and environmental sciences; Diet; Leucine; Obesity; Supplementation

Abstract

Excess dietary fat consumption has been implicated in the development of obesity and diabetes. Obesity can be characterized by a disproportionate increase in fat mass compared to lean body mass. However, if muscle mass can be increased or maintained in obesity, this may facilitate weight loss by increasing the body’s overall metabolic capacity. Historically, supplementation with the branched-chain amino acid leucine has been shown to increase muscle protein synthesis via the protein kinase mTORC1. Recent studies suggest that supplementation with leucine also has the potential to reduce weight gain and fat deposition in high-fat fed, obese mice. The objective of this study was to determine if long-term dietary leucine supplementation prevents development of obesity in rats meal-fed a high fat (60%) diet. Male, Sprague-Dawley rats (n=30/dietary treatment) were meal-fed (3 meals/day) either a control diet (C), control+leucine (CL), high-fat (HF), or high-fat+leucine (HFL) for 42 days. HF/HFL-fed rats gained, 28 g more than rats fed C/CL diets (p<0.05). Plasma insulin levels in the fasted condition were not significant between groups; however, thirty minutes postprandial the rats supplemented with leucine, both on a high-fat and control diet, had significantly higher insulin levels than the control group (p<0.05). Free fatty levels in the fasted condition did not differ between the control diet and the control diet with leucine supplementation. However, plasma free fatty acid levels in the fasted condition were significantly higher in the high-fat with leucine group when compared to the high-fat group without leucine supplementation (p<0.05). Rats supplemented with leucine had significantly higher fat mass (p<0.05) and significantly lower muscle mass (p<0.05) compared to their respective controls. No significant difference was detected in 4E-BP1 and AKT phosphorylation between diets or between time points. PGC-1α expression in fasted conditions did not differ between leucine supplemented groups and their respective controls. At 30 minutes postprandial, only the control diet with leucine supplementation was observed to have significantly greater PGC-1α expression than the high-fat diet with leucine supplementation (p<0.05). Taken together, supplementation with leucine does not prevent development of obesity in high-fat fed rats.

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