Summary Metabolomic profiling of obese versus lean humans reveals a branched-chain amino acid (BCAA)-related metabolite signature that is suggestive of increased catabolism of BCAA and correlated with insulin resistance. To test its impact on metabolic homeostasis, we fed rats on high-fat (HF), HF with supplemented BCAA (HF/BCAA) or standard chow (SC) diets. Despite having reduced food intake and weight gain equivalent to the SC group, HF/BCAA rats were equally insulin resistant as HF rats. Pair-feeding of HF diet to match the HF/BCAA animals or BCAA addition to SC diet did not cause insulin resistance. Insulin resistance induced by HF/BCAA feeding was accompanied by chronic phosphorylation of mTOR, JNK, and IRS1(ser307), accumulation of multiple acylcarnitines in muscle, and was reversed by the mTOR inhibitor, rapamycin. Our findings show that in the context of a poor dietary pattern that includes high fat consumption, BCAA contributes to development of obesity-associated insulin resistance.

EARLY TWO-THIRDS OF US adults are overweight or obese. 1 Together overweight and obesity are the second leading cause of preventable death, primarily through effects on car-diovascular disease (CVD) risk factors (hypertension, dyslipidemia, and type 2 diabetes). 2 Weight loss improves these risk factors, and evidence suggests that benefits persist as long as weight loss is maintained. [3][4][5][6][7][8] Relatively short-term (ie, 4-6 months) behavioral interventions for adults re-sult in clinically significant weight loss, but regain is an intractable problem. [9][10][11] Given the vast scope of the over-Author Affiliations are listed at the end of this article.

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.