1. p53-upregulated-modulator-of-apoptosis (PUMA) deficiency affects food intake but does not impact on body weight or glucose homeostasis in diet-induced obesity.
- Author
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Litwak SA, Loh K, Stanley WJ, Pappas EG, Wali JA, Selck C, Strasser A, Thomas HE, and Gurzov EN
- Subjects
- Adipose Tissue pathology, Animals, Apoptosis Regulatory Proteins genetics, Apoptosis Regulatory Proteins physiology, Diet, High-Fat adverse effects, Glucose Tolerance Test, Homeostasis physiology, Insulin pharmacology, Insulin Resistance, Leptin blood, Liver pathology, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Obesity pathology, Recombinant Proteins pharmacology, Tumor Suppressor Proteins genetics, Tumor Suppressor Proteins physiology, Apoptosis Regulatory Proteins deficiency, Body Weight physiology, Eating physiology, Glucose metabolism, Obesity physiopathology, Tumor Suppressor Proteins deficiency
- Abstract
BCL-2 proteins have been implicated in the control of glucose homeostasis and metabolism in different cell types. Thus, the aim of this study was to determine the role of the pro-apoptotic BH3-only protein, p53-upregulated-modulator-of-apoptosis (PUMA), in metabolic changes mediated by diet-induced obesity, using PUMA deficient mice. At 10 weeks of age, knockout and wild type mice either continued consuming a low fat chow diet (6% fat), or were fed with a high fat diet (23% fat) for 14-17 weeks. We measured body composition, glucose and insulin tolerance, insulin response in peripheral tissues, energy expenditure, oxygen consumption, and respiratory exchange ratio in vivo. All these parameters were indistinguishable between wild type and knockout mice on chow diet and were modified equally by diet-induced obesity. Interestingly, we observed decreased food intake and ambulatory capacity of PUMA knockout mice on high fat diet. This was associated with increased adipocyte size and fasted leptin concentration in the blood. Our findings suggest that although PUMA is dispensable for glucose homeostasis in lean and obese mice, it can affect leptin levels and food intake during obesity.
- Published
- 2016
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