Browsing by Author "Zhang, Christine"
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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 Effects of High Carbohydrate Supplementation on Hepatic Mitochondrial Metabolism(2020) Zhang, Christine; Sunny, NishanthNon-alcoholic fatty liver disease (NAFLD) is a major public health issue affecting over 75 million patients and over 70% of patients that suffer from Type 2 Diabetes Mellitus and obesity. Previous research has demonstrated that progression of NAFLD is accompanied by liver mitochondria adaptation and eventual dysfunction as they fail to respond to the influx of free fatty acids and the metabolic actions of insulin. The aim of this study was to elucidate the effects of high carbohydrate supplementation on mitochondrial metabolism, specifically the tricarboxylic acid (TCA) cycle, of hepatocytes utilizing a metabolomics centered approach. Data obtained through gas chromatography mass spectrometry (GC/MS) suggest that LF and HC fed animals exhibit higher mitochondrial (TCA) activity compared to their HF counterparts. Short-term increased mitochondrial activity suggests an increased robust metabolic response, however, long-term effects may be detrimental to metabolic flexibility through increased production of reactive oxygen species. While the comprehensive effects of high carbohydrate supplementation on metabolism are still under investigation, these results suggest that diets high in carbohydrates may lead to exacerbation of mitochondria, and ultimately metabolic dysfunction.