College of Agriculture & Natural Resources
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Item Dietary Macronutrient Composition Differentially Modulates the Remodeling of Mitochondrial Oxidative Metabolism during NAFLD(MDPI, 2021-04-26) Kattapuram, Nathan; Zhang, Christine; Muyyarikkandy, Muhammed S.; Surugihalli, Chaitra; Muralidaran, Vaishna; Gregory, Tabitha; Sunny, Nishanth E.Diets rich in fats and carbohydrates aggravate non-alcoholic fatty liver disease (NAFLD), of which mitochondrial dysfunction is a central feature. It is not clear whether a high-carbohydrate driven ‘lipogenic’ diet differentially affects mitochondrial oxidative remodeling compared to a high-fat driven ‘oxidative’ environment. We hypothesized that the high-fat driven ‘oxidative’ environment will chronically sustain mitochondrial oxidative function, hastening metabolic dysfunction during NAFLD. Mice (C57BL/6NJ) were reared on a low-fat (LF; 10% fat calories), high-fat (HF; 60% fat calories), or high-fructose/high-fat (HFr/HF; 25% fat and 34.9% fructose calories) diet for 10 weeks. De novo lipogenesis was determined by measuring the incorporation of deuterium from D2O into newly synthesized liver lipids using nuclear magnetic resonance (NMR) spectroscopy. Hepatic mitochondrial metabolism was profiled under fed and fasted states by the incubation of isolated mitochondria with [13C3]pyruvate, targeted metabolomics of tricarboxylic acid (TCA) cycle intermediates, estimates of oxidative phosphorylation (OXPHOS), and hepatic gene and protein expression. De novo lipogenesis was higher in the HFr/HF mice compared to their HF counterparts. Contrary to our expectations, hepatic oxidative function after fasting was induced in the HFr/HF group. This differential induction of mitochondrial oxidative function by the high fructose-driven ‘lipogenic’ environment could influence the progressive severity of hepatic insulin resistance.Item The Impacts of Branched Chain Amino Acid Supplementation on Adipocyte Function(2021) Gregory, Tabitha; Sunny, Nishanth E; Animal Sciences; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)The branched chain amino acids (BCAAs) are three essential amino acids: valine, leucine, and isoleucine. Adipose tissue has high rates of BCAA degradation and this has been shown to fuel normal function. Recent literature highlights cross- talk between BCAAs, lipid metabolism, and mitochondrial dysfunction. The objective of this thesis is to determine the impact of BCAA supplementation on adipose development, morphology, and various aspects of energy metabolism including BCAA degradation and lipolysis.C57-BL6N mice were reared on either low-fat (LF), LF with 150% BCAAs (LB), high-fat (HF), or HF with 150% BCAAs (HB) diets for 12-34 weeks. Adipose tissue morphology and energetics were determined. Results demonstrated that BCAA supplementation reduced lipid storage in visceral adipose depots, lowered circulating leptin, and reduced lipid accumulation in brown adipose tissue. BCAA supplementation also induced lipolysis, which raised circulating fatty acids. These results could have implications in the treatment and prevention of metabolic diseases.