PT  - JOURNAL ARTICLE
AU  - Nadejda Bozadjieva Kramer
AU  - Simon S. Evers
AU  - Jae Hoon Shin
AU  - Sierra Silverwood
AU  - Yibin Wang
AU  - Charles F. Burant
AU  - Darleen A. Sandoval
AU  - Randy J. Seeley
TI  - The role of elevated branched chain amino acids in the potent effects of vertical sleeve gastrectomy to reduce weight and improve glucose regulation in mice
AID  - 10.1101/2020.06.01.128157
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.06.01.128157
4099  - http://biorxiv.org/content/early/2020/06/02/2020.06.01.128157.short
4100  - http://biorxiv.org/content/early/2020/06/02/2020.06.01.128157.full
AB  - Obesity and type 2 diabetes mellitus (T2D) are growing epidemics resulting in increased morbidity and mortality. An emerging body of evidence has shown that elevated levels of branched-chain amino acids (BCAA) and their metabolites are strongly positively associated with obesity, insulin-resistance and T2D. Bariatric surgery is among the best treatments for weight loss and the alleviation of T2D. Additionally, clinical studies have reported that bariatric surgery decreases the circulating levels of BCAA. The objective of these studies was to test the hypothesis that reduced BCAA levels contribute to the metabolic improvements after VSG. We find that, as in humans, circulating BCAA levels are significantly lower in VSG rats and mice compared to Sham controls. In order to increase circulating BCAA levels, we tested mice with either increased dietary intake of BCAA or impaired BCAA catabolism by total body deletion of mitochondrial phosphatase 2C, Pp2cm, a key enzyme in the rate-limiting step in BCAA catabolism. Our results show that a decrease in circulating BCAA levels is not necessary for sustained body weight loss and improved glucose tolerance after VSG. While it is clear that circulating levels of BCAAs are excellent biomarkers for metabolic status, the current data do not support a causal role in determining metabolic regulation and the response to VSG.Competing Interest StatementRJS has received research support from Ethicon Endo-Surgery, Zafgen, Novo Nordisk, Kallyope, and MedImmune. RJS has served on scientific advisory boards for Ethicon Endo-Surgery, Novo Nordisk, Sanofi, Janssen, Kallyope, Scohia, and Ironwood Pharma. RJS is a stakeholder of Zafgen. SSE is a paid-employee of Gubra (Denmark).