Effects of individual branched-chain amino acids deprivation on insulin sensitivity and glucose metabolism in mice

Xiao, Fei; Yu, Junjie; Guo, Yinlong; Deng, Jiali; Li, Kai; Du, Ying; Chen, Shanghai; Zhu, Jie; Sheng, Hongguang; Guo, Feifan

doi:10.1016/j.metabol.2014.03.006

Cited by 88 publications

(69 citation statements)

References 37 publications

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“…In vivo , the infusion of AA, especially BCAA, reduces insulin sensitivity [10–12]. BCAA deprivation in rodents also improves insulin sensitivity in insulin resistant mice [13]. On the other hand, the rapid increase in insulin sensitivity and improvement in glucose homeostasis following weight loss surgery coincides with reductions in circulating BCAA, AAA, and several AA metabolites [14–16].…”

Section: Introductionmentioning

confidence: 99%

Effect of Insulin Sensitizer Therapy on Amino Acids and Their Metabolites

et al. 2015

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Aims Prior studies have reported that elevated concentrations of several plasma amino acids (AA) in plasma, particularly branched chain (BCAA) and aromatic AA predict the onset of type 2 diabetes. We sought to test the hypothesis that circulating BCAA, aromatic AA and related AA metabolites decline in response to the use of insulin sensitizing agents in overweight/obese adults with impaired fasting glucose or untreated diabetes. Methods We performed a secondary analysis of a randomized, double-blind, placebo, controlled study conducted in twenty five overweight/obese (BMI~30 kg/m2) adults with impaired fasting glucose or untreated diabetes. Participants were randomized to three months of pioglitazone (45 mg per day) plus metformin (1000 mg twice per day, N = 12 participants) or placebo (N = 13). We measured insulin sensitivity by the euglycemic-hyperinsulinemic clamp and fasting concentrations of AA and AA metabolites using ultra-pressure liquid chromatography tandem mass spectrometry before and after the three-month intervention. Results Insulin sensitizer therapy that significantly enhanced insulin sensitivity reduced 9 out of 33 AA and AA metabolites measured compared to placebo treatment. Moreover, insulin sensitizer therapy significantly reduced three functionally clustered AA and metabolite pairs: i) phenylalanine/tyrosine, ii) citrulline/arginine, and iii) lysine/α-aminoadipic acid. Conclusions Reductions in plasma concentrations of several AA and AA metabolites in response to three months of insulin sensitizer therapy support the concept that reduced insulin sensitivity alters AA and AA metabolites.

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Section: Introductionmentioning

confidence: 99%

Effect of Insulin Sensitizer Therapy on Amino Acids and Their Metabolites

et al. 2015

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“…This is the first evidence that a physiological and sustainable reduction of dietary BCAAs can promote health and glycemic control, but it is not the first evidence that dietary BCAAs have an important role in metabolic health. Several studies have observed increased serum levels of the three BCAAs in insulin-resistant humans and animals, and BCAA levels are predictive of development of type 2 diabetes (reviewed in (Lynch and Adams, 2014)), while feeding mice a diet entirely lacking in either leucine, isoleucine, or valine promotes insulin sensitivity (Xiao et al, 2011; Xiao et al, 2014). Feeding a diet with reduced levels of BCAAs to Zucker fatty rats likewise improves skeletal muscle insulin sensitivity (White et al).…”

Section: Branched Chain Amino Acids Regulate Metabolic Healthmentioning

confidence: 99%

“…As discussed above, GCN2 is a major sensor of amino acid deficiency which regulates translation via the phosphorylation of eIF2α. The catabolism of BCAAs is also a major source of energy, and restriction of either dietary protein or of the BCAAs specifically can result in the activation of AMPK (Chotechuang et al, 2009; Xiao et al, 2014). Likewise, while methionine is essential for protein translation and can be utilized for energy, it also has a key role in numerous cellular processes following conversion to the methyl donor S-adenosylmethionine (SAM) (Brosnan and Brosnan, 2006).…”

Section: Branched Chain Amino Acids Regulate Metabolic Healthmentioning

confidence: 99%

Regulation of metabolic health and aging by nutrient-sensitive signaling pathways

Cummings

Lamming

2017

Molecular and Cellular Endocrinology

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All organisms need to be capable of adapting to changes in the availability and composition of nutrients. Over 75 years ago, researchers discovered that a calorie restricted (CR) diet could significantly extend the lifespan of rats, and since then a CR diet has been shown to increase lifespan and healthspan in model organisms ranging from yeast to non-human primates. In this review, we discuss the effects of a CR diet on metabolism and healthspan, and highlight emerging evidence that suggests that dietary composition – the precise macronutrients that compose the diet – may be just as important as caloric content. In particular, we discuss recent evidence that suggests protein quality may influence metabolic health. Finally, we discuss key metabolic pathways which may influence the response to CR diets and altered macronutrient composition. Understanding the molecular mechanisms responsible for the effects of CR and dietary composition on health and longevity may allow the design of novel therapeutic approaches to age-related diseases.

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“…Young mice fed a leucine-deficient diet showed increased insulin sensitivity, reduced mTOR signaling, and activated GCN2 signaling (136,137). A decrease in fat mass, increased lipolysis, increased energy expenditure, increased insulin sensitivity, downregulation of mTOR signaling, and upregulation of AMP kinase (AMPK) signaling were found in young mice fed diets deficient in either isoleucine or valine (137,138).…”

Section: Limitation Of Essential Amino Acids and Growth In Animal Modelsmentioning

confidence: 99%

“…A decrease in fat mass, increased lipolysis, increased energy expenditure, increased insulin sensitivity, downregulation of mTOR signaling, and upregulation of AMP kinase (AMPK) signaling were found in young mice fed diets deficient in either isoleucine or valine (137,138).…”

Section: Limitation Of Essential Amino Acids and Growth In Animal Modelsmentioning

confidence: 99%

Perspective: The Potential Role of Essential Amino Acids and the Mechanistic Target of Rapamycin Complex 1 (mTORC1) Pathway in the Pathogenesis of Child Stunting

Semba

Trehan

González-Freire

et al. 2016

Advances in Nutrition

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Stunting is the best summary measure of chronic malnutrition in children. Approximately one-quarter of children under age 5 worldwide are stunted. Lipid-based or micronutrient supplementation has little to no impact in reducing stunting, which suggests that other critical dietary nutrients are missing. A dietary pattern of poor-quality protein is associated with stunting. Stunted children have significantly lower circulating essential amino acids than do nonstunted children. Inadequate dietary intakes of essential amino acids could adversely affect growth, because amino acids are required for synthesis of proteins. The master growth regulation pathway, the mechanistic target of rapamycin complex 1 (mTORC1) pathway, is exquisitely sensitive to amino acid availability. mTORC1 integrates cues such as nutrients, growth factors, oxygen, and energy to regulate growth of bone, skeletal muscle, nervous system, gastrointestinal tract, hematopoietic cells, immune effector cells, organ size, and whole-body energy balance. mTORC1 represses protein and lipid synthesis and cell and organismal growth when amino acids are deficient. Over the past 4 decades, the main paradigm for child nutrition in developing countries has been micronutrient malnutrition, with relatively less attention paid to protein. In this Perspective, we present the view that essential amino acids and the mTORC1 pathway play a key role in child growth. The current assumption that total dietary protein intake is adequate for growth among most children in developing countries needs reevaluation. Adv Nutr 2016;7:853-65.

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Effects of individual branched-chain amino acids deprivation on insulin sensitivity and glucose metabolism in mice

Cited by 88 publications

References 37 publications

Effect of Insulin Sensitizer Therapy on Amino Acids and Their Metabolites

Effect of Insulin Sensitizer Therapy on Amino Acids and Their Metabolites

Regulation of metabolic health and aging by nutrient-sensitive signaling pathways

Perspective: The Potential Role of Essential Amino Acids and the Mechanistic Target of Rapamycin Complex 1 (mTORC1) Pathway in the Pathogenesis of Child Stunting

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