Alterations in branched-chain amino acid kinetics in nonobese but insulin-resistant Asian men

• Published in: The American journal of clinical nutrition Vol. 108; no. 6; pp. 1220 - 1228
• Main Authors: Tan, Hong Chang, Hsu, Jean W, Khoo, Chin Meng, Tai, E Shyong, Yu, Sidney, Chacko, Shaji, Lai, Oi Fah, Jahoor, Farook
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.12.2018; Oxford University Press; American Society for Clinical Nutrition, Inc
• Subjects: Abnormalities; Adipose tissue; adiposity; Adult; Amino acids; Amino Acids, Branched-Chain - blood; Amino Acids, Branched-Chain - pharmacokinetics; Asian People; Asians; Blood Glucose - analysis; Body composition; branched chain amino acids; Carbon Isotopes; Chain branching; Chains; deuterium oxide; Diabetes mellitus; Diet; Dietary intake; dietary protein; Dilution; fasting; Fatty acids; Fatty Acids, Nonesterified - blood; Fatty Acids, Nonesterified - pharmacokinetics; Fluctuations; Flux; free fatty acids; Glucose; Glucose tolerance; Glucose Tolerance Test; glucose tolerance tests; Humans; Insulin; Insulin - blood; Insulin resistance; Insulin Resistance - physiology; Isotopes; Kinetics; Leucine; Leucine - pharmacokinetics; leucine and free fatty acid oxidation; Male; Men; Mens health; Metabolism; nonobese Asian men; Oxidation; Oxidation-Reduction; palmitates; Palmitic acid; Palmitic Acid - pharmacokinetics; protein intake; Proteins; stable isotopes; stable-isotope kinetics; Substrates; tracer techniques; Tracers; FFA; leucine and free fatty acid oxidation; NOD; T2D; α-KICA; IR; IS; branched-chain amino acids; Ra; stable-isotope kinetics; PDH; VCO2; IE; OGTT; insulin resistance; WBIS; nonobese Asian men; BCAA; RQ
• ISSN: 0002-9165; 1938-3207; 1938-3207
• DOI: 10.1093/ajcn/nqy208

Branched-chain amino acids (BCAAs) are elevated in the insulin-resistant (IR) state. The reasons for this increase remain unclear, but it may be related to abnormalities in BCAA metabolism and free fatty acid (FFA) metabolism. In this study, we quantified BCAA and FFA kinetics of IR and insulin-sensitive (IS) nonobese Asian men with the use of stable-isotope tracers. We hypothesized that in addition to greater substrate flux, the BCAA oxidative pathway is also impaired to account for the higher plasma BCAA concentration in the IR state. We recruited 12 IR and 14 IS nonobese and healthy Asian men. Oral-glucose-tolerance tests (OGTTs) were performed to quantify insulin sensitivity, and subjects underwent 2 stable-isotope infusion studies. [U-13C6]Leucine was infused to measure leucine flux and oxidation as indexes of BCAA metabolism, whereas [U-13C16]palmitate was infused to measure palmitate flux and oxidation to represent FFA metabolism, The 2H2O dilution method was used to estimate body composition. IR subjects had greater adiposity and significantly higher fasting and post-OGTT glucose and insulin concentrations compared with the IS group. However, none of the subjects were diabetic. Despite similar dietary protein intake, IR subjects had a significantly higher plasma BCAA concentration and greater leucine flux. Leucine oxidation was also greater in the IR group, but the relation between leucine oxidation and flux was significantly weaker in the IR group than in the IS group (r = 0.530 compared with 0.695, P < 0.0388 for differences between slope). FFA oxidation was, however, unaffected despite higher FFA flux in the IR group. The higher plasma BCAA concentration in healthy nonobese individuals with IR is associated with a weaker relation between BCAA oxidation and BCAA flux and this occurs in the presence of accelerated FFA flux and oxidation.