Abstract
BackgroundLeucine supplementation might have therapeutic potential in preventing diet-induced obesity and improving insulin sensitivity. However, the underlying mechanisms are at present unclear. Additionally, it is unclear whether leucine supplementation might be equally efficacious once obesity has developed.Methodology/Principal FindingsMale C57BL/6J mice were fed chow or a high-fat diet (HFD), supplemented or not with leucine for 17 weeks. Another group of HFD-fed mice (HFD-pairfat group) was food restricted in order to reach an adiposity level comparable to that of HFD-Leu mice. Finally, a third group of mice was exposed to HFD for 12 weeks before being chronically supplemented with leucine. Leucine supplementation in HFD-fed mice decreased body weight and fat mass by increasing energy expenditure, fatty acid oxidation and locomotor activity in vivo. The decreased adiposity in HFD-Leu mice was associated with increased expression of uncoupling protein 3 (UCP-3) in the brown adipose tissue, better insulin sensitivity, increased intestinal gluconeogenesis and preservation of islets of Langerhans histomorphology and function. HFD-pairfat mice had a comparable improvement in insulin sensitivity, without changes in islets physiology or intestinal gluconeogenesis. Remarkably, both HFD-Leu and HFD-pairfat mice had decreased hepatic lipid content, which likely helped improve insulin sensitivity. In contrast, when leucine was supplemented to already obese animals, no changes in body weight, body composition or glucose metabolism were observed.Conclusions/SignificanceThese findings suggest that leucine improves insulin sensitivity in HFD-fed mice by primarily decreasing adiposity, rather than directly acting on peripheral target organs. However, beneficial effects of leucine on intestinal gluconeogenesis and islets of Langerhans's physiology might help prevent type 2 diabetes development. Differently, metabolic benefit of leucine supplementation is lacking in already obese animals, a phenomenon possibly related to the extent of the obesity before starting the supplementation.
Highlights
Healthy eating is critical for health and well-being
The decrease in body weight gain observed in high-fat diet (HFD)-Leu mice was due to a decrease in fat mass (Figure 1C), while no changes were observed in lean mass (Figure 1D) or food intake as compared to HFD-water animals (Figure 1B)
The present study demonstrates that dietary leucine prevents HFD-induced obesity by increasing energy expenditure, locomotor activity and fatty acid oxidation in vivo, leading to decreased adiposity and better insulin sensitivity
Summary
Healthy eating is critical for health and well-being. despite the evident logic of such a statement, it is a fact that nutrition-related diseases, such as obesity are currently on the rise. Diet composition strongly influences metabolic changes that lead to obesity and its associated diseases, including diabetes, dyslipidemia and cancer [1]. The consumption of western diets, which are rich in saturated fats and sugars, favors obesity, and plays a significant role in the development of insulin resistance [2]. Manipulation of macronutrient content has an important impact on energy balance regulation and on health, since macronutrients do represent fuel substrates and work as signaling molecules able to affect cellular metabolic processes [5]. Leucine supplementation might have therapeutic potential in preventing diet-induced obesity and improving insulin sensitivity. The underlying mechanisms are at present unclear. It is unclear whether leucine supplementation might be efficacious once obesity has developed
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