Adipose tissue monomethyl branched-chain fatty acids and insulin sensitivity: Effects of obesity and weight loss

Abstract

Objectives: An increase in circulating branched-chain amino acids (BCAA) is associated with insulin resistance. Adipose tissue is a potentially important site for BCAA metabolism. It was evaluated whether monomethyl branched-chain fatty acids (mmBCFA) in adipose tissue, which are likely derived from BCAA catabolism, are associated with insulin sensitivity.

Methods: Insulin-stimulated glucose disposal was determined by using the hyperinsulinemic-euglycemic clamp procedure with stable isotope glucose tracer infusion in nine lean and nine obese subjects, and in a separate group of nine obese subjects before and 1 year after Roux-en-Y gastric bypass (RYGB) surgery (38% weight loss). Adipose tissue mmBCFA content was measured in tissue biopsies taken in the basal state.

Results: Total adipose tissue mmBCFA content was ∼30% lower in obese than lean subjects (P=0.02) and increased by ∼65% after weight loss in the RYGB group (P=0.01). Adipose tissue mmBCFA content correlated positively with skeletal muscle insulin sensitivity (R(2) =35%, P=0.01, n=18).

Conclusions: These results demonstrate a novel association between adipose tissue mmBCFA content and obesity-related insulin resistance. Additional studies are needed to determine whether the association between adipose tissue mmBCFA and muscle insulin sensitivity is causal or a simple association.

Figure 1

Subcutaneous abdominal adipose tissue total mmBCFA content (A) and C16:0 and C18:1 (n-9) contents (B) (as percentages of total fatty acids), and FAS gene expression (C) in lean (black) and obese (white) subjects. *Value is significantly different from corresponding value in lean subjects, P = 0.02. Values are means ± SEM (n = 9).

Figure 2

Individual and group means of subcutaneous abdominal adipose tissue total mmBCFA content (A) and FAS gene expression (B) in obese subjects before (white) and 1 year after (black) weight loss induced by Roux-en-Y gastric bypass surgery. Value is significantly different from corresponding value before surgery, *P = 0.05, **P = 0.01. Values are means ± SEM (n = 9).

Figure 3

Relationship between skeletal muscle insulin sensitivity, assessed as insulin-stimulated glucose rate of disappearance (Rd) from plasma during a hyperinsulinemic-euglycemic clamp procedure and subcutaneous abdominal adipose tissue total mmBCFA content in 18 lean (black squares) and obese (white circles) subjects (A), and relationship between weight loss-induced changes in adipose tissue total mmBCFA content and insulin-stimulated glucose Rd in a separate group of 9 extremely obese subjects (B).