Effects of prolonged fasting on AMPK signaling, gene expression, and mitochondrial respiratory chain content in skeletal muscle from lean and obese individuals

Abstract

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.

Obesity is marked by distinct functional connectivity in brain networks involved in food reward and salience

“…It must be noted that we did not control for menstrual cycle and/or contraceptive use, which might have affected our results. Hormonal parameters and heart rate variability were assessed as well and have been previously published [28,58]. Due to the timing of these measurements, it is not possible to correlate these data directly with the fMRI data.…”

“…On the first study day, subjects underwent baseline MRI scanning. After the MRI, participants consumed a standardized breakfast and then fasted for the next 48 h. The ingestion of breakfast was necessary for measuring other parameters, skeletal muscle biopsies and blood sampling, published elsewhere [28]. Drinking water and noncaffeinated tea was allowed ad libitum.…”

A 5-Day High-Fat, High-Calorie Diet Impairs Insulin Sensitivity in Healthy, Young South Asian Men but Not in Caucasian Men

“…A complete overview of all analyzed genes can be found in Supplementary (36). Blots were quantified by densitometric analysis using ImageJ software (National Institutes of Health).…”

Middle-aged overweight South Asian men exhibit a different metabolic adaptation to short-term energy restriction compared with Europeans

“…Western blots were performed using phospho-specific ( [19]. Blots were quantified by densitometric analysis using Image J software (ImageJ, NIH, Bethesda, Maryland, USA).…”