Associations between plasma branched-chain amino acids, β-aminoisobutyric acid and body composition.
Plasma branched-chain amino acids (BCAA) are elevated in obesity and associated with increased cardiometabolic risk. β-Aminoisobutyric acid (B-AIBA), a recently identified small molecule metabolite, is associated with decreased cardiometabolic risk. Therefore, we investigated the association of BCAA and B-AIBA with each other and with detailed body composition parameters, including abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT). A cross-sectional study was carried out with lean (n 15) and obese (n 33) men and women. Detailed metabolic evaluations, including measures of body composition, insulin sensitivity and plasma metabolomics were completed. Plasma BCAA were higher (1·6 (se 0·08) (×10(7)) v. 1·3 (se 0·06) (×10(7)) arbitrary units; P = 0·005) in obese v. lean subjects. BCAA were positively associated with VAT (R 0·49; P = 0·0006) and trended to an association with SAT (R 0·29; P = 0·052). The association between BCAA and VAT, but not SAT, remained significant after controlling for age, sex and race on multivariate modelling (P < 0·05). BCAA were also associated with parameters of insulin sensitivity (Matsuda index: R -0·50, P = 0·0004; glucose AUC: R 0·53, P < 0·001). BCAA were not associated with B-AIBA (R -0·04; P = 0·79). B-AIBA was negatively associated with SAT (R -0·37; P = 0·01) but only trended to an association with VAT (R 0·27; P = 0·07). However, neither relationship remained significant after multivariate modelling (P > 0·05). Plasma B-AIBA was associated with parameters of insulin sensitivity (Matsuda index R 0·36, P = 0·01; glucose AUC: R -0·30, P = 0·04). Plasma BCAA levels were positively correlated with VAT and markers of insulin resistance. The results suggest a possible complex role of adipose tissue in BCAA homeostasis and insulin resistance.
Division of Human Nutrition , Wageningen University , NL-6703 HD Wageningen , The Netherlands.
Annemarie
A
Rietman
Program in Nutritional Metabolism and Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Pediatric Endocrine Unit, Massachusetts General Hospital, Boston, MA 02114, USA.
Takara L
TL
Stanley
Broad Institute of MIT and Harvard , Cambridge , MA 02142 , USA.
Clary
C
Clish
Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Center for Human Genetic Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Vamsi
V
Mootha
Division of Human Nutrition , Wageningen University , NL-6703 HD Wageningen , The Netherlands.
Marco
M
Mensink
Program in Nutritional Metabolism and Neuroendocrine Unit , Massachusetts General Hospital and Harvard Medical School , Boston , MA 02114 , USA.
Steven K
SK
Grinspoon
Program in Nutritional Metabolism and Neuroendocrine Unit , Massachusetts General Hospital and Harvard Medical School , Boston , MA 02114 , USA.
Hideo
H
Makimura
AU, arbitrary units; B-AIBA, β-aminoisobutyric acid; BCAA, branched-chain amino acid; BCAT, branched-chain amino acid aminotransferase; BCKD, branched-chain α-ketoacid dehydrogenase; Branched-chain amino acids; DXA, dual-energy X-ray absorptiometry; HOMA-IR, homeostasis model assessment for insulin resistance; Lean body mass; Metabolomics; OGTT, oral glucose tolerance test; SAT, subcutaneous adipose tissue; Subcutaneous adipose tissue; VAT, visceral adipose tissue; Visceral adiposity; β-Aminoisobutyric acid