A Branched-Chain Amino Acid-Related Metabolic Signature that Differentiates Obese and Lean Humans and Contributes to Insulin Resistance

Abstract

In preparation of the paper, there were several errors in the figure labeling, which were regretfully missed in the preparation and proofreading of the manuscript and which the authors would like to correct. None of these changes affects the data or the conclusions of the paper.(1) The heading of Figure 2H should read ''Glucose Infusion Rate,'' not ''Insulin Infusion Rate.'' (2) In the corresponding text on page 431 (right column, paragraph 2, line 13), the units for glucose infusion rate should be ''mg/kg/min,'' not ''mg/dl.'' (3) Likewise, on the y axis in Figure 2I, the units for glucose should read ''mg/kg/min'' rather than ''mg/dl.'' (4) On the y axis in Figures 3C, 4F, 4G, 4H, and 5D, the parenthetical reference to ''ARNT/Actin'' carried over from previous figures should simply be deleted. The correct specific genes or proteins measured in each panel are already indicated. (5) In Figure 5A, the correct units are ''mM,'' not ''mM/l.

Insulin resistance and the metabolism of branched-chain amino acids in humans

“…Consequently, the postabsorptive plasma concentration of BCAAs, phenylalanine, and tyrosine has been detected elevated in obese patients compared with nonobese individuals (Felig et al 1969a, b;Caballero and Wurtman 1991;Solini et al 1997;Chevalier et al 2005Chevalier et al , 2006She et al 2007;Newgard et al 2009;Huffman et al 2009). Recently, the elevated concentration of BCAAs in overweight and obese patients has been independently associated with insulin resistance and linearly related to the homeostasis model assessment (HOMA) index of insulin resistance (Newgard et al 2009;Huffman et al 2009). Additionally, weight loss results in a fall in serum insulin and a concomitant reduction in the concentration of BCAAs, phenylalanine, and tyrosine (She et al 2007).…”

Genetics of Abdominal Obesity

“…rs1558902. Previous studies have shown associations between branched amino acids (BCAAs) or aromatic amino acids (AAAs) with obesity, insulin sensitivity, and incident type 2 diabetes mellitus (T2DM) [96][97][98] and weight loss induced by gastric bypass surgery or behavioral/dietary intervention [99,100]. In the POUNDS LOST trial, investigators found a significant interaction between the amino acid metabolite-related genotype rs1440581 (PPM1K) [101] and dietary fat on weight loss and changes in insulin resistance [102].…”

Essential Amino Acid Supplementation for the Prevention and Treatment of Obesity

“…By metabolic profiling, Newgard et al [155] studied subjects that become obese on a typical Western diet. In these subjects, circulating levels of BCAAs were higher in obese than in lean subjects [155].…”

“…By metabolic profiling, Newgard et al [155] studied subjects that become obese on a typical Western diet. In these subjects, circulating levels of BCAAs were higher in obese than in lean subjects [155]. Obesity was also associated with decreased availability of insulin-like growth factor I (IGF-I), thus suggesting that overnutrition and low IGF-I levels are associated with increased circulating BCAA and that the subsequent overload of BCAA catabolism contributes to insulin resistance in obese subjects.…”