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Plasma Amino Acids Stimulate Uncoupled Respiration of Muscle Subsarcolemmal Mitochondria in Lean but Not Obese Humans.

ABSTRACT: Obesity is associated with mitochondrial dysfunction in skeletal muscle. Increasing the plasma amino acid (AA) concentrations stimulates mitochondrial adenosine triphosphate (ATP) production in lean individuals.To determine whether acute elevation in plasma AAs enhances muscle mitochondrial respiration and ATP production in subsarcolemmal (SS) and intermyofibrillar (IMF) mitochondria in obese adults.Assessment of SS and IMF mitochondrial function during saline (i.e., control) and AA infusions.Eligible participants were healthy lean (body mass index, <25 kg/m2; age, 37 ± 3 years; n = 10) and obese (body mass index >30 kg/m2; age 35 ± 3 years; n = 11) subjects.Single trial of saline infusion followed by AA infusion. SS and IMF mitochondria were isolated from muscle biopsies collected at the end of the saline and AA infusions.Mitochondrial respiration and ATP production.AA infusion increased adenosine 5'-diphosphate (ADP)-stimulated respiration and ATP production rates of SS mitochondria in the lean (P < 0.05), but not obese, subjects. Furthermore, AA infusion increased the uncoupled (i.e., non-ADP-stimulated) respiration of SS mitochondria in the lean subjects only (P < 0.05). AA infusion had no effect on any of these parameters in IMF mitochondria in either lean or obese subjects (P > 0.05).Increasing the plasma AA concentrations enhances the capacity for respiration and ATP production of muscle SS, but not IMF, mitochondria in lean individuals, in parallel with increases in uncoupled respiration. However, neither of these parameters increases in muscle SS or IMF mitochondria in obese individuals.

SUBMITTER: Kras KA

PROVIDER: S-EPMC5718694 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Plasma Amino Acids Stimulate Uncoupled Respiration of Muscle Subsarcolemmal Mitochondria in Lean but Not Obese Humans.

Kras Katon A KA Hoffman Nyssa N Roust Lori R LR Patel Shivam H SH Carroll Chad C CC Katsanos Christos S CS

The Journal of clinical endocrinology and metabolism 20171201 12

<h4>Context</h4>Obesity is associated with mitochondrial dysfunction in skeletal muscle. Increasing the plasma amino acid (AA) concentrations stimulates mitochondrial adenosine triphosphate (ATP) production in lean individuals.<h4>Objective</h4>To determine whether acute elevation in plasma AAs enhances muscle mitochondrial respiration and ATP production in subsarcolemmal (SS) and intermyofibrillar (IMF) mitochondria in obese adults.<h4>Design</h4>Assessment of SS and IMF mitochondrial function ...[more]

PMID: 29029131

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Project description:Background & aimsDysbiosis of the gut microbiota in response to an energy-rich Western diet and the potential leak of bacteria and/or bacterial products from the intestine to the liver is perceived as a potential risk factor for the development of non-alcoholic fatty liver disease (NAFLD). We investigated the microbiome in liver biopsies from healthy lean and obese individuals and compared it with their blood microbiome.MethodsWe examined liver biopsies from 15 healthy lean and 14 obese individuals (BMI of 18.5-25 and 30-40 kg/m2, respectively). Bacterial 16S ribosomal DNA (rDNA) was analysed by quantitative polymerase chain reaction (qPCR) and 16S metagenomic sequencing targeting the hypervariable V3-V4 region. Metagenomic analysis was performed using the linear discriminant analysis effect size (LEfSe) algorithm. Data are medians with IQRs in brackets.ResultsHistology revealed hepatic steatosis in 13 obese individuals and in 2 lean individuals. A robust signal from qPCR revealed significantly higher amounts of bacterial rDNA copies in liver samples from obese individuals compared with those from lean individuals (148 [118-167] vs. 77 [62-122] 16S copies/ng DNA, p <0.001). Liver biopsies from the obese group were characterised by lower alpha diversity at the phylum level (Shannon index 0.60 [0.55-0.76] vs. 0.73 [0.62-0.90], p = 0.025), and metagenomic profiling revealed a significantly higher proportion of Proteobacteria in this group (81.0% [73.0-82.4%] vs. 74.3% [68.4-78.4%], p = 0.014).ConclusionsWe provide evidence for the presence of bacterial rDNA in the healthy human liver. Based on differences in the hepatic microbiome between obese individuals and healthy lean individuals, we suggest that changes in the liver microbiome could constitute an additional risk factor for the development of NAFLD.Lay summaryNon-alcoholic fatty liver disease (NAFLD) has become the most common liver disease globally, and new evidence suggests that obesity is associated with a disturbed gut bacterial composition, which may influence the development of NAFLD. We examined the composition of bacterial DNA in liver biopsies from healthy lean and obese individuals and found a different composition of bacterial DNA in liver biopsies from the obese group. We propose that the increased bacterial DNA load in the livers of obese individuals could constitute an early risk factor for the progression of NAFLD.Clinical trial numberNCT02337660.

Dataset Information

Plasma Amino Acids Stimulate Uncoupled Respiration of Muscle Subsarcolemmal Mitochondria in Lean but Not Obese Humans.

Publications

Plasma Amino Acids Stimulate Uncoupled Respiration of Muscle Subsarcolemmal Mitochondria in Lean but Not Obese Humans.

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