Effects of prolonged fasting on AMPK signaling, gene expression, and mitochondrial respiratory chain content in skeletal muscle from lean and obese individuals
| Autor: | Gerard C.M. van der Zon, Marjolein A. Wijngaarden, Bruno Guigas, Ko Willems van Dijk, Hanno Pijl |
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| Rok vydání: | 2013 |
| Předmět: |
Adult
Male AMPK medicine.medical_specialty fasting Physiology Endocrinology Diabetes and Metabolism Blotting Western Gene Expression AMP-Activated Protein Kinases Mitochondrion Real-Time Polymerase Chain Reaction Electron Transport metabolic flexibility Lipid oxidation Antigens CD Physiology (medical) Internal medicine medicine Humans Obesity skeletal muscle Muscle Skeletal Heat-Shock Proteins biology Leptin Body Weight Skeletal muscle Calorimetry Indirect medicine.disease Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha Receptor Insulin Mitochondria Muscle mitochondria Insulin receptor Glucose medicine.anatomical_structure Endocrinology Mitochondrial respiratory chain Body Composition biology.protein Female Lipid Peroxidation Signal Transduction Transcription Factors |
| Zdroj: | AJP-Endocrinology and Metabolism, 304(9), E1012-E1021 |
| ISSN: | 1522-1555 0193-1849 |
| DOI: | 10.1152/ajpendo.00008.2013 |
| Popis: | Obesity in humans is often associated with metabolic inflexibility, but the underlying molecular mechanisms remain incompletely understood. The aim of the present study was to investigate how adaptation to prolonged fasting affects energy/nutrient-sensing pathways and metabolic gene expression in skeletal muscle from lean and obese individuals. Twelve lean and 14 nondiabetic obese subjects were fasted for 48 h. Whole body glucose/lipid oxidation rates were determined by indirect calorimetry, and blood and skeletal muscle biopsies were collected and analyzed. In response to fasting, body weight loss was similar in both groups, but the decrease in plasma insulin and leptin and the concomitant increase in growth hormone were significantly attenuated in obese subjects. The fasting-induced shift from glucose toward lipid oxidation was also severely blunted. At the molecular level, the expression of insulin receptor-β (IRβ) was lower in skeletal muscle from obese subjects at baseline, whereas the fasting-induced reductions in insulin signaling were similar in both groups. The protein expression of mitochondrial respiratory chain components, although not modified by fasting, was significantly reduced in obese subjects. Some minor differences in metabolic gene expression were observed at baseline and in response to fasting. Surprisingly, fasting reduced AMPK activity in lean but not in obese subjects, whereas the expression of AMPK subunits was not affected. We conclude that whole body metabolic inflexibility in response to prolonged fasting in obese humans is associated with lower skeletal muscle IRβ and mitochondrial respiratory chain content as well as a blunted decline of AMPK activity. |
| Databáze: | OpenAIRE |
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