Dataset Information

Leucine supplementation improves acquired growth hormone resistance in rats with protein-energy malnutrition.

ABSTRACT:

Background

Protein-energy malnutrition (PEM) can lead to growth hormone (GH) resistance. Leucine supplementation diets have been shown to increase protein synthesis in muscles. Our study aimed at investigating if long-term leucine supplementation could modulate GH-insulin-like growth factor (IGF)-1 system function and mammalian target of rapamycin (mTOR)-related signal transduction in skeletal muscles in a rat model of severe malnutrition.

Methodology/principal findings

Male Sprague-Dawley rats (n = 50; weight, 302 ± 5 g) were divided into 5 treatment groups, including 2 control groups (a normal control group that was fed chow and ad libitum water [CON, n = 10] and a malnourished control group [MC, n = 10] that was fed a 50% chow diet). After undergoing a weight loss stage for 4 weeks, rats received either the chow diet (MC-CON, n = 10), the chow diet supplemented with low-dose leucine (MC-L, n = 10), or the chow diet supplemented with high-dose leucine (MC-H, n = 10) for 2 weeks. The muscle masses of the gastrocnemius, soleus, and extensor digitorum longus were significantly reduced in the MC group. Re-feeding increased muscle mass, especially in the MC-L and MC-H groups. In the MC group, serum IGF-1, IGF-binding protein (IGFBP)-3, and hepatic growth hormone receptor (GHR) levels were significantly decreased and phosphorylation of the downstream anabolic signaling effectors protein kinase B (Akt), mTOR, and ribosomal protein S6 kinase 1 (S6K1) were significantly lower than in other groups. However, serum IGF-1 and IGF binding protein (IGFBP)-3 concentrations and hepatic growth hormone receptor (GHR) levels were significantly higher in the MC-L and MC-H groups than in the MC-CON group, and serum IGFBP-1 levels was significantly reduced in the MC-L and MC-H groups. These changes were consistent with those observed for hepatic mRNA expression levels. Phosphorylation of the downstream anabolic signaling effectors Akt, mTOR, and S6K1 were also significantly higher in the MC-L and MC-H groups than in the MC-CON group.

Conclusion/significance

Our data are the first to demonstrate that long-term supplementation with leucine improved acquired growth hormone resistance in rats with protein-energy malnutrition. Leucine might promote skeletal muscle protein synthesis by regulating downstream anabolic signaling transduction.

SUBMITTER: Gao X

PROVIDER: S-EPMC4409315 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Publications

Leucine supplementation improves acquired growth hormone resistance in rats with protein-energy malnutrition.

Gao Xuejin X Tian Feng F Wang Xinying X Zhao Jie J Wan Xiao X Zhang Li L Wu Chao C Li Ning N Li Jieshou J

PloS one 20150424 4

<h4>Background</h4>Protein-energy malnutrition (PEM) can lead to growth hormone (GH) resistance. Leucine supplementation diets have been shown to increase protein synthesis in muscles. Our study aimed at investigating if long-term leucine supplementation could modulate GH-insulin-like growth factor (IGF)-1 system function and mammalian target of rapamycin (mTOR)-related signal transduction in skeletal muscles in a rat model of severe malnutrition.<h4>Methodology/principal findings</h4>Male Sprag ...[more]

PMID: 25909895

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Project description:Recommendations concerning protein quantity, source, and leucine intake for older adults are difficult to reach by regular dietary intake. This randomized clinical trial assesses in sarcopenic community-dwelling older adults (i) the regular (non-supplemented) daily protein and leucine intake; and (ii) the effect of personalized protein supplementation (aiming for an evenly distributed total protein intake of 1.5 g·kg-1·d-1 of body mass, accounting for energy intake) on regular and total (dietary and supplemental) intake. A preliminary feasibility study in participants of the ongoing Exercise and Nutrition for Healthy AgeiNg (ENHANce) study was performed with the objective to assess the intake and distribution of regular dietary protein and leucine, protein source and energy intake in (pre)sarcopenic community-dwelling older adults. Moreover, this study aimed to assess if personalized protein supplementation was feasible without negatively affecting regular dietary intake. ENHANce (NCT03649698) is a 5-armed RCT that assesses the effect of anabolic interventions on physical performance in (pre)sarcopenic older adults. In August 2019, n = 51 participants were included in ENHANce with complete available data on dietary intake at screening and thus eligible for inclusion in present analysis. Of these, n = 35 participants completed the intervention period of ENHANce at the moment of analysis, allowing an exploration of the effect of supplementation on regular dietary intake. The regular dietary protein intake of 51 (pre)sarcopenic adults (73.6 ± 6.5 years) was 1.06 ± 0.3 g·kg-1·d-1 of body mass. Protein supplementation (n = 20) improved total protein intake to 1.55 ± 0.3 g·kg-1·d-1 of body mass (P < 0.001) without affecting regular dietary protein (P = 0.176) or energy intake (P = 0.167). Placebo supplementation (n = 15) did not affect regular dietary protein intake (P = 0.910) but decreased regular dietary energy intake (P = 0.047). Regular leucine intake was unevenly distributed over the day, but increased by supplementation at breakfast (P < 0.001) and dinner (P = 0.010) to at least 2.46 g leucine·meal-1, without reducing regular dietary leucine intake (P = 0.103). Animal-based protein intake-the main protein source-was not affected by supplementation (P = 0.358). Personalized protein supplementation ensured an adequate quantity and even distribution of protein and leucine over the day, without affecting regular dietary protein or energy intake.

Project description: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.

Dataset Information

Leucine supplementation improves acquired growth hormone resistance in rats with protein-energy malnutrition.

Background

Methodology/principal findings

Conclusion/significance

Publications

Leucine supplementation improves acquired growth hormone resistance in rats with protein-energy malnutrition.

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