Dataset Information

Coordinated Modulation of Energy Metabolism and Inflammation by Branched-Chain Amino Acids and Fatty Acids.

ABSTRACT: As important metabolic substrates, branched-chain amino acids (BCAAs) and fatty acids (FAs) participate in many significant physiological processes, such as mitochondrial biogenesis, energy metabolism, and inflammation, along with intermediate metabolites generated in their catabolism. The increased levels of BCAAs and fatty acids can lead to mitochondrial dysfunction by altering mitochondrial biogenesis and adenosine triphosphate (ATP) production and interfering with glycolysis, fatty acid oxidation, the tricarboxylic acid cycle (TCA) cycle, and oxidative phosphorylation. BCAAs can directly activate the mammalian target of rapamycin (mTOR) signaling pathway to induce insulin resistance, or function together with fatty acids. In addition, elevated levels of BCAAs and fatty acids can activate the canonical nuclear factor-?B (NF-?B) signaling pathway and inflammasome and regulate mitochondrial dysfunction and metabolic disorders through upregulated inflammatory signals. This review provides a comprehensive summary of the mechanisms through which BCAAs and fatty acids modulate energy metabolism, insulin sensitivity, and inflammation synergistically.

SUBMITTER: Ye Z

PROVIDER: S-EPMC7506139 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Coordinated Modulation of Energy Metabolism and Inflammation by Branched-Chain Amino Acids and Fatty Acids.

Ye Zhenhong Z Wang Siyu S Zhang Chunmei C Zhao Yue Y

Frontiers in endocrinology 20200908

As important metabolic substrates, branched-chain amino acids (BCAAs) and fatty acids (FAs) participate in many significant physiological processes, such as mitochondrial biogenesis, energy metabolism, and inflammation, along with intermediate metabolites generated in their catabolism. The increased levels of BCAAs and fatty acids can lead to mitochondrial dysfunction by altering mitochondrial biogenesis and adenosine triphosphate (ATP) production and interfering with glycolysis, fatty acid oxid ...[more]

PMID: 33013697

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Project description:IntroductionHypoglycemia is a major limiting factor in achieving recommended glycemic targets for people with type 1 diabetes. Exposure to recurrent hypoglycemia results in blunted hormonal counter-regulatory and symptomatic responses to hypoglycemia. Limited data on metabolic adaptation to recurrent hypoglycemia are available. This study examined the acute metabolic responses to hypoglycemia and the effect of antecedent hypoglycemia on these responses in type 1 diabetes.Research design and methodsTwenty-one outpatients with type 1 diabetes with normal or impaired awareness of hypoglycemia participated in a study assessing the response to hypoglycemia on 2 consecutive days by a hyperinsulinemic glucose clamp. Participants underwent a period of normoglycemia and a period of hypoglycemia during the hyperinsulinemic glucose clamp. Plasma samples were taken during normoglycemia and at the beginning and the end of the hypoglycemic period. Metabolomic analysis of the plasma samples was conducted using comprehensive two-dimensional gas chromatography with time-of-flight mass spectrometry.ResultsIn total, 68 metabolites were studied. On day 1, concentrations of the branched-chain amino acids, leucine (p=3.8×10-3) and isoleucine (p=2.2×10-3), decreased during hypoglycemia. On day 2, during hypoglycemia, five amino acids (including leucine and isoleucine) significantly decreased, and two fatty acids (tetradecanoic and oleic acids) significantly increased (p<0.05). Although more metabolites responded to hypoglycemia on day 2, the responses of the single metabolites were not statistically significant between the 2 days.ConclusionsIn individuals with type 1 diabetes, one episode of hypoglycemia decreases leucine and isoleucine concentrations. Antecedent hypoglycemia results in the decrement of five amino acids and increases the concentrations of two fatty acids, suggesting an alteration between the two hypoglycemic episodes, which could indicate a possible adaptation. However, more studies are needed to gain a comprehensive understanding of the consequences of these alterations.Trial registration numberNCT01337362.

Dataset Information

Coordinated Modulation of Energy Metabolism and Inflammation by Branched-Chain Amino Acids and Fatty Acids.

Publications

Coordinated Modulation of Energy Metabolism and Inflammation by Branched-Chain Amino Acids and Fatty Acids.

Similar Datasets

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