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The role of brown adipose tissue in branched-chain amino acid clearance in people.

ABSTRACT: Brown adipose tissue (BAT) in rodents appears to be an important tissue for the clearance of plasma branched-chain amino acids (BCAAs) contributing to improved metabolic health. However, the role of human BAT in plasma BCAA clearance is poorly understood. Here, we evaluate patients with prostate cancer who underwent positron emission tomography-computed tomography imaging after an injection of ¹⁸F-fluciclovine (L-leucine analog). Supraclavicular adipose tissue (AT; primary location of human BAT) has a higher net uptake rate for ¹⁸F-fluciclovine compared to subcutaneous abdominal and upper chest AT. Supraclavicular AT ¹⁸F-fluciclovine net uptake rate is lower in patients with obesity and type 2 diabetes. Finally, the expression of genes involved in BCAA catabolism is higher in the supraclavicular AT of healthy people with high BAT volume compared to those with low BAT volume. These findings support the notion that BAT can potentially function as a metabolic sink for plasma BCAA clearance in people.

SUBMITTER: Abdelhafez YG

PROVIDER: S-EPMC11340589 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature

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The role of brown adipose tissue in branched-chain amino acid clearance in people.

Abdelhafez Yasser G YG Wang Guobao G Li Siqi S Pellegrinelli Vanessa V Chaudhari Abhijit J AJ Ramirez Anthony A Sen Fatma F Vidal-Puig Antonio A Sidossis Labros S LS Klein Samuel S Badawi Ramsey D RD Chondronikola Maria M

iScience 20240720 8

Brown adipose tissue (BAT) in rodents appears to be an important tissue for the clearance of plasma branched-chain amino acids (BCAAs) contributing to improved metabolic health. However, the role of human BAT in plasma BCAA clearance is poorly understood. Here, we evaluate patients with prostate cancer who underwent positron emission tomography-computed tomography imaging after an injection of <sup>18</sup>F-fluciclovine (L-leucine analog). Supraclavicular adipose tissue (AT; primary location of ...[more]

PMID: 39175781

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Project description:Background: Predicting relapses of post-operative complications in obese patients who undergo cardiac surgery is significantly complicated by persistent metabolic maladaptation associated with obesity. Despite studies supporting the linkages of increased systemic branched-chain amino acids (BCAAs) driving the pathogenesis of obesity, metabolome wide studies have either supported or challenged association of circulating BCAAs with cardiovascular diseases (CVDs). Objective: We interrogated whether BCAA catabolic changes precipitated by obesity in the heart and adipose tissue can be reliable prognosticators of adverse outcomes following cardiac surgery. Our study specifically clarified the correlation between BCAA catabolizing enzymes, cellular BCAAs and branched-chain keto acids (BCKAs) with the severity of cardiometabolic outcomes in obese patients pre and post cardiac surgery. Methods: Male and female patients of ages between 44 and 75 were stratified across different body mass index (BMI) (non-obese = 17, pre-obese = 19, obese class I = 14, class II = 17, class III = 12) and blood, atrial appendage (AA), and subcutaneous adipose tissue (SAT) collected during cardiac surgery. Plasma and intracellular BCAAs and BC ketoacids (BCKAs), tissue mRNA and protein expression and activity of BCAA catabolizing enzymes were assessed and correlated with clinical parameters. Results: Intramyocellular, but not systemic, BCAAs increased with BMI in cardiac surgery patients. In SAT, from class III obese patients, mRNA and protein expression of BCAA catabolic enzymes and BCKA dehydrogenase (BCKDH) enzyme activity was decreased. Within AA, a concomitant increase in mRNA levels of BCAA metabolizing enzymes was observed, independent of changes in BCKDH protein expression or activity. BMI, indices of tissue dysfunction and duration of hospital stay following surgery correlated with BCAA metabolizing enzyme expression and metabolite levels in AA and SAT. Conclusion: This study proposes that in a setting of obesity, dysregulated BCAA catabolism could be an effective surrogate to determine cardiac surgery outcomes and plausibly predict premature re-hospitalization.

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The role of brown adipose tissue in branched-chain amino acid clearance in people.

Publications

The role of brown adipose tissue in branched-chain amino acid clearance in people.

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