Early Metabolic Adaptation in C57BL/6 Mice Resistant to High Fat Diet Induced Weight Gain Involves an Activation of Mitochondrial Oxidative Pathways

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• 作者：Claire L. Boulang茅 ; Sandrine P. Claus ; Chieh J. Chou ; Sebastiano Collino ; Ivan Montoliu ; Sunil Kochhar ; Elaine Holmes ; Serge Rezzi ; Jeremy K. Nicholson ; Marc E. Dumas ; Fran莽ois-Pierre J. Martin
• 刊名：Journal of Proteome Research
• 出版年：2013
• 出版时间：April 5, 2013
• 年：2013
• 卷：12
• 期：4
• 页码：1956-1968
• 全文大小：664K
• 年卷期：v.12,no.4(April 5, 2013)
• ISSN：1535-3907

文摘

We investigated the short-term (7 days) and long-term (60 days) metabolic effect of high fat diet induced obesity (DIO) and weight gain in isogenic C57BL/6 mice and examined the specific metabolic differentiation between mice that were either strong-responders (SR), or non-responders (NR) to weight gain. Mice (n = 80) were fed a standard chow diet for 7 days prior to randomization into a high-fat (HF) (n = 56) or a low-fat (LF) (n = 24) diet group. The ¹H NMR urinary metabolic profiles of LF and HF mice were recorded 7 and 60 days after the diet switch. On the basis of the body weight gain (BWG) distribution of HF group, we identified NR mice (n = 10) and SR mice (n = 14) to DIO. Compared with LF, HF feeding increased urinary excretion of glycine conjugates of 尾-oxidation intermediate (hexanoylglycine), branched chain amino acid (BCAA) catabolism intermediates (isovalerylglycine, 伪-keto-尾-methylvalerate and 伪-ketoisovalerate) and end-products of nicotinamide adenine dinucleotide (NAD) metabolism (N1-methyl-2-pyridone-5-carboxamide, N1-methyl-4-pyridone-3-carboxamide) suggesting up-regulation of mitochondrial oxidative pathways. In the HF group, NR mice excreted relatively more hexanoylglycine, isovalerylglycine, and fewer tricarboxylic acid (TCA) cycle intermediate (succinate) in comparison to SR mice. Thus, subtle regulation of ketogenic pathways in DIO may alleviate the saturation of the TCA cycle and mitochondrial oxidative metabolism.

Keywords:

diet-induced obesity; obesity-prone mice; obesity-resistant mice; ¹H NMR metabolic profiles; BCAA catabolism; 尾-oxidation; mitochondria