Abstract
Objectives
Branched chain amino acids (BCAAs), Valine, Leucine, and Isoleucine have been shown to impact adipose tissue physiology through regulation of adipocyte differentiation, lipogenesis, and lipolysis. Further, circulating BCAAs are elevated during obesity and insulin resistance, a characteristic attributed to impaired BCAA catabolic networks in adipose tissue and skeletal muscle. The objective of this study was to determine whether the induction of lipolysis in adipose tissue is a characteristic feature prompted by the chronic availability of BCAAs.
Methods
Mice (C57-BL6N) were kept on low-fat (LF, 10% fat calories; n = 9) and low-fat supplemented with 150% BCAA (LB; n = 10) diets for 34 weeks. Following an overnight fast (∼12–14 hrs), serum and perigonadal adipose (PGA) tissue samples were collected for metabolic analysis. Serum free fatty acids (FFAs) were analyzed and 25 milligrams (mg) of PGA was used for an in vitro lipolysis assay. Lipolysis in the PGA was induced under basal
and isoproterenol (ISP, 10 micromolar, μM) stimulated conditions for 2 hours. In a second experiment, PGA tissue explants from normal mice (n = 18) were incubated with two levels of BCAA supplementation (500 μM and 1 millimolar, mM). FFAs in the incubation media were measured as an index of adipose tissue lipolysis.
Results
Overnight fasting body weights of the LF and LB mice remained similar. However, PGA tissue weights were significantly lower in the LB group (grams ± SEM; LF, 1.34 ± 0.09 vs LB, 0.84 ± 0.11, P = 0.003). LB serum FFAs were elevated (mM FFAs ± SEM; LF 0.73 ± 0.04 vs LB, 0.88 ± 0.04, P = 0.01). Basal lipolysis (mM FFAs/mg tissue protein ± SEM) trended to be higher in the PGA from the LB animals (LF, 1.44 ± 0.18 vs LB, 1.88 ± 0.15, P = 0.08). While ISP significantly induced lipolysis, the stimulated lipolytic rates remained similar between LF and LB groups. When normal PGA explants were challenged with BCAAs, the 1mM BCAA supplemented group tended to show higher fatty acid release (mM FFAs/mg tissue protein ± SEM; 500 μM, 0.89 ± 0.06 vs 1mM, 1.02 ± 0.05, P = 0.09).
Conclusions
In summary, these results suggest that BCAA mediated increases in adipose tissue lipolysis can contribute to circulating FFA levels. BCAA mediated lipolysis and the subsequent increase in circulating FFAs could indirectly modulate substrate oxidation in peripheral tissues including liver and muscle.
Funding Sources
NIH RO1