Abstract
Obesity is a major health problem, and although caloric restriction and exercise are successful strategies to lose adipose tissue in obese individuals, a simultaneous decrease in skeletal muscle mass, negatively effects metabolism and muscle function. To deeper understand molecular events occurring in muscle during weight-loss, we measured the expressional change in human skeletal muscle following a combination of severe caloric restriction and exercise over 4 days in 15 Swedish men. Key metabolic genes were regulated after the intervention, indicating a shift from carbohydrate to fat metabolism. Nicotinamide N-methyltransferase (NNMT) was the most consistently upregulated gene following the energy-deficit exercise. Circulating levels of N1-methylnicotinamide (MNA), the product of NNMT activity, were doubled after the intervention. The fasting-fed state was an important determinant of plasma MNA levels, peaking at ~18 h of fasting and being lowest ~3 h after a meal. In culture, MNA was secreted by isolated human myotubes and stimulated lipolysis directly, with no effect on glucagon or insulin secretion. We propose that MNA is a novel myokine that enhances the utilization of energy stores in response to low muscle energy availability. Future research should focus on applying MNA as a biomarker to identify individuals with metabolic disturbances at an early stage.
Highlights
The number of individuals who are overweight or obese is increasing worldwide and obesity elevates the risk of many serious diseases, including certain forms of cancer, cardiovascular disease and type 2 diabetes (T2D)
Nicotinamide N-methyltransferase (NNMT) was upregulated 5.4, 4.2 and 2.9-fold at WCR compared with PRE in non-exercised and exercised arm and leg muscles, respectively
We examined changes in skeletal muscle gene expression after caloric restriction in combination with an exercise intervention
Summary
The number of individuals who are overweight or obese is increasing worldwide and obesity elevates the risk of many serious diseases, including certain forms of cancer, cardiovascular disease and type 2 diabetes (T2D). The reduction in body mass was sustained (4.4 kg) four weeks after the intervention and the relative reduction in fat mass was increased to 90% (3.8 kg) of the total decrease in body mass. The majority of this reduction (~70%) was accounted for by loss of trunk fat, leading to a diminished waist circumference (~7 cm). A significant reduction in body weight (2.4 kg) was maintained a year after the intervention, most of which (~80%) was due to loss of fat mass This weight reduction was accompanied by improvements in blood lipids, e.g. reduced total cholesterol and low-density lipoprotein levels. The aim of the present study was to examine changes in gene expression in skeletal muscle in response to exercise combined with severe energy deficit
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