Protective Effects of Glutamine and Leucine Supplementation on Sepsis-Induced Skeletal Muscle Injuries

This study investigated the effects of l-glutamine (Gln) and/or l-leucine (Leu) administration on sepsis-induced skeletal muscle injuries. C57BL/6J mice were subjected to cecal ligation and puncture to induce polymicrobial sepsis and then given an intraperitoneal injection of Gln, Leu, or Gln plus Leu beginning at 1 h after the operation with re-injections every 24 h. All mice were sacrificed on either day 1 or day 4 after the operation. Blood and muscles were collected for analysis of inflammation and oxidative damage-related biomolecules. Results indicated that both Gln and Leu supplementation alleviated sepsis-induced skeletal muscle damage by reducing monocyte infiltration, calpain activity, and mRNA expression levels of inflammatory cytokines and hypoxia-inducible factor-1α. Furthermore, septic mice treated with Gln had higher percentages of blood anti-inflammatory monocytes and muscle M2 macrophages, whereas Leu treatment enhanced the muscle expressions of mitochondrion-related genes. However, there were no synergistic effects when Gln and Leu were simultaneously administered. These findings suggest that both Gln and Leu had prominent abilities to attenuate inflammation and degradation of skeletal muscles in the early and/or late phases of sepsis. Moreover, Gln promoted the switch of leukocytes toward an anti-inflammatory phenotype, while Leu treatment maintained muscle bioenergetic function.

Pyruvate Might Bridge Gut Microbiota and Muscle Health in Aging Mice After Chronic High Dose of Leucine Supplementation

Background: The previous studies demonstrated that there might be complex and close relationships among leucine supplementation, gut microbiota, and muscle health, which still needs further investigation.Aims: This study aimed to explore the associations of gut microbiota with muscle health after leucine intake.Methods: In this study, 19-month-old male C57BL/6j mice (n = 12/group) were supplemented with ultrapure water, low dose of leucine (500 mg/kg·d), and high dose of leucine (1,250 mg/kg·d) for 12 weeks by oral gavage. The mice fecal samples in each group before and after supplementation were collected for baseline and endpoint gut microbiota analysis by using 16S rDNA amplicon sequencing. Meanwhile, ultrasound measurement, H&E staining, myofiber cross-sectional area (CSA) measurement, and western blotting were performed in the quadriceps subsequently. The pyruvate levels were detected in feces.Results: Improvement in muscle of histology and ultrasonography were observed after both low and high dose of leucine supplementation. High dose of leucine supplementation could promote skeletal muscle health in aging mice via regulating AMPKα/SIRT1/PGC-1α. The richness and diversities of microbiota as well as enriched metabolic pathways were altered after leucine supplementation. Firmicutes-Bacteroidetes ratio was significantly decreased in high-leucine group. Moreover, pyruvate fermentation to propanoate I were negatively associated with differential species and the pyruvate levels were significantly increased in feces after high dose of leucine supplementation.Conclusions: Chronic high dose of leucine supplementation changed gut microbiota composition and increased pyruvate levels in the feces, which possibly provides a novel direction for promoting muscle health in aging mice.

Leucine supplementation during late gestation globally altered placental metabolism and nutrient transport via modulation of the PI3K/AKT/mTOR signalling pathway

Background Our previous study found that sow dietary leucine supplementation signicicantly improved fetal intrauterine growth and newborn piglet birth weight. But we still have limited knowledge how leucine regulated placental functions to promote the nutrient supply to fetus to support its intrauterine development. Methods 150 sows at day 90 of gestiation were divided into three groups and fed with either control diet (CON), CON + 0.4% Leu or CON + 0.8% Leu separately until parturition. Placental metabolomics, full spectrum amino acids and nutrient transporters were systematically analyzed. Results Leu supplementation lead to an altered placental metabolism with higher amount of metabolites related to glycolysis and fatty acids oxidatation, and more amino acids accumulation in placenta. Besides, nutrient transporters including amino acids transporters, glucose transporters and fatty acids transporters in placenta were globally enhanced and several enzymes related to energy metabolism including hexokinase, succinatede hydrogenase, lactated hydrogenase, glycogen phosphorylase and hydroxyaryl-CoA-dehydrogenase were significantly increased with no change in antioxidative status in the groups with Leu supplementation. Futhermore, Leu supplementation significantly increased phosphalation of PI3K, Akt, and mTOR in placenta compared with control group. Conclusions Leu supplementation during late gestation globally altered placental metabolism, nutrient transport (amino acids, glucose, and fatty acids) via modulation of the PI3K/Akt/mTOR signalling pathway.

L-Leucine Improves Metabolic Disorders in Mice With in-utero Cigarette Smoke Exposure

Objectives: Maternal cigarette smoke exposure (SE) causes intrauterine undernutrition, resulting in increased risk for metabolic disorders and type 2 diabetes in the offspring without sex differences. L-leucine supplementation has been shown to reduce body weight and improve glucose metabolism in both obese animals and humans. In this study, we aimed to determine whether postnatal L-leucine supplementation in female offspring can ameliorate the detrimental impact of maternal SE.Methods: Female Balb/c mice (6-week) were exposed to cigarette smoke (SE, 2 cigarettes/day) prior to mating for 5 weeks until the pups weaned. Sham dams were exposed to air during the same period. Half of the female offspring from the SE and SHAM dams were supplied with L-leucine via drinking water (1.5% w/w) after weaning (21-day) for 10 weeks and sacrificed at 13 weeks (adulthood).Results: Maternal SE during pregnancy resulted in smaller body weight and glucose intolerance in the offspring. L-leucine supplement in Sham offspring reduced body weight, fat mass, and fasting blood glucose levels compared with their untreated littermates; however somatic growth was not changed. L-leucine supplement in SE offspring improved glucose tolerance and reduced fat mass compared with untreated littermates.Conclusions: Postnatal L-leucine supplement could reduce fat accumulation and ameliorate glucose metabolic disorder caused by maternal SE. The application of leucine may provide a potential strategy for reducing metabolic disorders in offspring from mothers who continued to smoke during pregnancy.

Different Effects of Leucine Supplementation and/or Exercise on Systemic Insulin Sensitivity in Mice

ObjectiveObesity-related diseases such as diabetes, hypertension, dyslipidemia, and cardiovascular diseases have increased due to the obesity epidemic. Early intervention for obesity through lifestyle and nutrition plays an important role in preventing obesity-related diseases. Therefore, the purpose of this study is to explore the role of leucine and exercise in adiposity, systemic insulin resistance, and inflammation to provide theoretical and guiding basis for the early prevention and treatment of obesity.MethodsC57BL/6J male mice were randomly divided into HFD or LFD-fed mice group. After 9 weeks, glucose tolerance test (GTT) was performed to detect their systemic insulin sensitivity. Starting from week 10, mice were divided into eight groups and treated with moderate exercise or/and 1.5% leucine. At week 13, systemic insulin sensitivity was detected by GTT. At week 14, mice were dissected to analyze adiposity and inflammation.ResultsIn LFD mice, exercise significantly increased systemic insulin sensitivity by increasing GLUT4 expression in the muscle and decreasing adiposity through increasing AMPK phosphorylation in adipose tissue. In HFD mice, the simultaneous intervention of exercise and leucine increases systemic insulin sensitivity by reducing liver and adipose tissue inflammation via decreasing NF-κB p65 phosphorylation, and increasing the expression of adiponectin in adipose tissue.ConclusionThere are different mechanisms underlying the effects of exercise and leucine on insulin resistance and inflammation in LFD-fed mice or HFD-fed mice.

L-Leucine Supplementation for Preserving Lean Mass During Low Calorie Diet in Sarcopenic Obese Women: A Pilot Study

Background: In sarcopenic obese subjects it is essential to reduce body weight and to preserve lean mass, in order to avoid a worsening of muscle function (1). Several studies have shown that leucine supplementation can be useful to improve skeletal muscle mass in sarcopenic patients (2). Aim: Evaluate the effectiveness of a short-term low calorie diet (LCD) combined with combined supplementation with whey protein, leucine and vitamin D on weight loss, lean mass and muscle strength in sarcopenic, obese, hyperinsulinemic and menopause women. Materials and methods: 16 female with mean age: 58.1 years (range: 47–69 years), BMI 37.6 Kg/m2 (range: 31,7 - 44,1 Kg/m2), HOMA-index ≥ 2.5, were assigned to an LCD regimen (1000 kcal/day) with supplementation of 18 g protein, 4 g leucine and 5 mcg vitamin D for 45 days. Anthropometric indexes, blood and urine chemistry, body composition by DEXA, muscle strength by handgrip test and Short Physical Performance Battery (SPPB) were assessed at baseline and at the end of the treatment. Results: A significant reduction of BMI (35,7 vs 37,6 Kg/m2), waist circumference (102,4 vs 107 cm), HOMA index (2,3 vs 4,8) and fasting insulin (10,4 vs 17,4 μIU/ml) was observed in all patients. Women preserved total lean body mass (57 vs 55 %) and improved significantly muscle strength, as measured by handgrip (22,2 vs 18,6 Kg) and SPPB (8,9 vs 7,5). Conclusion: We conclude that LCD with adequate protein intake and a supplementation with whey protein, leucine and vitamin D should be promoted to maintain muscle mass and improve muscle strength in menopause women with sarcopenic obesity. References: 1. Batsis JA, Villareal DT. Sarcopenic obesity in older adults: aetiology, epidemiology and treatment strategies. Nat Rev Endocrinol. 2018 Sep;14(9):513–5372. Bauer JM, Verlaan S, Bautmans I, Brandt K, Donini LM, Maggio M, McMurdo ME, Mets T, Seal C, Wijers SL, Ceda GP, De Vito G, Donders G, Drey M, Greig C, Holmbäck U, Narici M, McPhee J, Poggiogalle E, Power D, Scafoglieri A, Schultz R, Sieber CC, Cederholm T. Effects of a vitamin D and leucine-enriched whey protein nutritional supplement on measures of sarcopenia in older adults, the PROVIDE study: a randomized, double-blind, placebo-controlled trial. J Am Med Dir Assoc. 2015 Sep 1;16(9)