The Role of Elevated Branched-Chain Amino Acids in the Effects of Vertical Sleeve Gastrectomy to Reduce Weight and Improve Glucose Regulation

Cell Rep. 2020 Oct 13;33(2):108239. doi: 10.1016/j.celrep.2020.108239.

Abstract

Elevated levels of branched-chain amino acids (BCAAs) and their metabolites are strongly positively associated with obesity, insulin resistance, and type 2 diabetes. Bariatric surgery is among the best treatments for weight loss and associated morbidities. Clinical studies have reported that bariatric surgery decreases the circulating levels of BCAAs. The objective of this study was to test the hypothesis that reduced BCAA levels contribute to the metabolic improvements of sustained weight loss and improved glucose tolerance after vertical sleeve gastrectomy (VSG). We find that, as in humans, circulating BCAAs are significantly lower in VSG rats and mice. To increase circulating BCAAs, we tested mice with either increased dietary intake of BCAAs or impaired BCAA catabolism by total body deletion of mitochondrial phosphatase 2C (Pp2cm). Our results show that a decrease in circulating BCAAs is not necessary for sustained body weight loss and improved glucose tolerance after VSG.

Keywords: BCAA; BCAA catabolism; Vertical Sleeve Gastrectomy; bariatric surgery; metabolism; type 2 diabetes.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Absorption, Physiological
  • Adipose Tissue, White / metabolism
  • Administration, Oral
  • Amino Acid Transport System y+L / metabolism
  • Amino Acids, Branched-Chain / administration & dosage
  • Amino Acids, Branched-Chain / blood
  • Amino Acids, Branched-Chain / metabolism*
  • Animals
  • Blood Circulation
  • Diet, High-Fat
  • Dietary Supplements
  • Epididymis / metabolism
  • Feeding Behavior
  • Gastrectomy*
  • Glucose / administration & dosage
  • Glucose / metabolism*
  • Male
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Protein Phosphatase 2C / metabolism
  • Rats, Long-Evans
  • Weight Loss*

Substances

  • Amino Acid Transport System y+L
  • Amino Acids, Branched-Chain
  • Slc7a7 protein, mouse
  • PPM1A protein, human
  • Protein Phosphatase 2C
  • Glucose