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

An, 2004, Hepatic expression of malonyl-CoA decarboxylase reverses muscle, liver and whole-animal insulin resistance, Nat. Med., 10, 268, 10.1038/nm995

Ashley, 1985, Evidence for diminished brain 5-hydroxytryptamine biosynthesis in obese diabetic and non-diabetic humans, Am. J. Clin. Nutr., 42, 1240, 10.1093/ajcn/42.6.1240

Bergman, 1981, Physiologic evaluation of factors controlling glucose tolerance in man: measurement of insulin sensitivity and beta-cell glucose sensitivity from the response to intravenous glucose, J. Clin. Invest., 68, 1456, 10.1172/JCI110398

Bjorbaek, 2004, Leptin signaling in the central nervous system and periphery, Recent Prog. Horm. Res., 59, 305, 10.1210/rp.59.1.305

Breum, 2003, Twenty-four hour plasma tryptophan concentrations and ratios are below normal in obese subjects and are not normalized by substantial weight reduction, Am. J. Clin. Nutr., 77, 1112, 10.1093/ajcn/77.5.1112

Cao, 2008, Identification of a lipokine, a lipid hormone linking adipose tissue to systemic metabolism, Cell, 134, 933, 10.1016/j.cell.2008.07.048

Capuron, 2002, Association between decreased serum tryptophan concentrations and depressive symptoms in cancer patients undergoing cytokine therapy, Mol. Psychiatry, 7, 468, 10.1038/sj.mp.4000995

Chace, 1995, Rapid diagnosis of maple syrup urine disease in blood spots from newborns by tandem mass spectrometry, Clin. Chem., 41, 62, 10.1093/clinchem/41.1.62

Chevalier, 2005, Whole-body protein anabolic response is resistant to the action of insulin in obese women, Am. J. Clin. Nutr., 82, 355, 10.1093/ajcn/82.2.355

Cota, 2006, Hypothalamic mTOR signaling regulates food intake, Science, 312, 927, 10.1126/science.1124147

Craig, 2003, International Physical Activity Questionnaire: 12-country reliability and validity, Med. Sci. Sports Exerc., 35, 1381, 10.1249/01.MSS.0000078924.61453.FB

Felig, 1974, Splanchnic glucose and amino acid metabolism in obesity, J. Clin. Invest., 53, 582, 10.1172/JCI107593

Fernstrom, 2005, Branched-chain amino acids and brain function, J. Nutr., 135, 1539S, 10.1093/jn/135.6.1539S

Ferrara, 2008, Genetic network of liver metabolism revealed by integration of metabolic and transcriptional profiling, PLoS Genet., 14, e1000034, 10.1371/journal.pgen.1000034

Gougeon, 2008, Determinants of whole-body protein metabolism in subjects with and without type 2 diabetes, Diabetes Care, 231, 128, 10.2337/dc07-1268

Haqq, 2005, The Study of the Effects of Diet on Metabolism and Nutrition (STEDMAN) weight loss project: rationale and design, Contemp. Clin. Trials, 26, 616, 10.1016/j.cct.2005.09.003

Harlan, 1990, Use of adjustment factors with a brief food frequency questionnaire to obtain nutrient values, Epidemiology, 1, 224, 10.1097/00001648-199005000-00008

He, 2006, Molecular disruption of hypothalamic nutrient sensing induces obesity, Nat. Neurosci., 9, 227, 10.1038/nn1626

Hedley, 2004, Prevalence of overweight and obesity among US children, adolescents, and adults, 1999-2002, JAMA, 291, 2847, 10.1001/jama.291.23.2847

Hiratani, 2005, Role of mTOR and JNK in serine phosphorylation, translocation and degradation of IRS-1, Biochem. Biophys. Res. Commun., 30, 836, 10.1016/j.bbrc.2005.07.152

Hosoda, 2006, Biological, physiological, and pharmacological aspects of ghrelin, J. Pharmacol. Sci., 100, 398, 10.1254/jphs.CRJ06002X

Houmard, 2002, Effect of weight loss on insulin sensitivity and intramuscular long-chain fatty acyl-CoAs in morbidly obese subjects, Diabetes, 51, 2959, 10.2337/diabetes.51.10.2959

Kahn, 2006, Obesity is a major determinant of the association of C-reactive protein levels and the metabolic syndrome in type 2 diabetes, Diabetes, 55, 2357, 10.2337/db06-0116

Koves, 2008, Mitochondrial overload and incomplete fatty acid oxidation contribute to skeletal musle insulin resistance, Cell Metab., 7, 45, 10.1016/j.cmet.2007.10.013

Krebs, 2002, Mechanism of amino acid-induced skeletal muscle insulin resistance in humans, Diabetes, 51, 599, 10.2337/diabetes.51.3.599

Krebs, 2003, Direct and indirect effects of amino acids on hepatic glucose metabolism in humans, Diabetologia, 46, 917, 10.1007/s00125-003-1129-1

Krebs, 2007, The mammalian target of rapamycin pathway regulates nutrient-sensitive glucose uptake in man, Diabetes, 56, 1600, 10.2337/db06-1016

Layman, 2006, Potential importance of leucine in treatment of obesity and the metabolic syndrome, J. Nutr., 136, 319S, 10.1093/jn/136.1.319S

Lepage, 1986, Direct transesterification of all classes of lipids in a one-step reaction, J. Lipid Res., 27, 114, 10.1016/S0022-2275(20)38861-1

Maccario, 1999, Relationship bewteen IGF-1 and age, gender, body mass, fat distribution, metabolic and hormonal variables in obese patients, Int. J. Obes. Relat. Metab. Disord., 23, 612, 10.1038/sj.ijo.0800889

Maccario, 2001, Effects of short-term administration of low-dose rhGH on IGF-1 levels in obesity and Cushing's syndrome: indirect evaluation of sensitivity to GH, Eur. J. Endocrinol., 144, 251, 10.1530/eje.0.1440251

Marin, 1993, Low concentrations of insulin-like growth factor-1 in abdominal obesity, Int. J. Obes. Relat. Metab. Disord., 17, 83

McGarry, 2002, Banting lecture 2001: dysregulation of fatty acid metabolism in the etiology of type 2 diabetes, Diabetes, 51, 607, 10.2337/diabetes.51.1.7

Millington, 1990, Tandem mass spectrometry: a new method for acylcarnitine profiling with potential for neonatal screening for inborn errors of metabolism, J. Inherit. Metab. Dis., 13, 321, 10.1007/BF01799385

Morino, 2006, Molecular mechanisms of insulin resistance in humans and their potential links with mitochondrial dysfunction, Diabetes, Suppl. 2, S9, 10.2337/db06-S002

Muoio, 2008, Molecular and metabolic mechanisms of insulin resistance and β-cell failure in type 2 diabetes, Nat. Rev. Mol. Cell Biol., 9, 193, 10.1038/nrm2327

Mussig, 2005, Insulin-induced stimulation of JNK and the PI 3-kinase/mTOR pathway leads to phosphorylation of serine 318 or IRS-1 in C2C12 myocytes, Biochem. Biophys. Res. Commun., 335, 819, 10.1016/j.bbrc.2005.07.154

Newgard, 2001, Substrate control in insulin release, 125

Patterson, 1999, Validation of a new procedure to determine plasma fatty acid concentration and isotopic enrichment, J. Lipid Res., 40, 2118, 10.1016/S0022-2275(20)32435-4

Pereira, 2008, Insulin resistance of protein metabolism in type 2 diabetes, Diabetes, 57, 56, 10.2337/db07-0887

Pocai, 2006, Restoration of hypothalamic lipid sensing normalizes energy and glucose homeostasis in overfed rats, J. Clin. Invest., 116, 1081, 10.1172/JCI26640

Rasmussen, 1994, The impact of obesity, fat distribution, and energy restriction on insulin-like growth factor-1, IGF binding protein-3, insulin, and growth hormone, Metabolism, 43, 315, 10.1016/0026-0495(94)90099-X

Reaven, 2006, The metabolic syndrome: is this diagnosis necessary?, Am. J. Clin. Nutr., 83, 1237, 10.1093/ajcn/83.6.1237

Ridker, 1998, Prospective study of C-reactive protein and the risk of future cardiovascular events among apparently healthy women, Circulation, 98, 731, 10.1161/01.CIR.98.8.731

Scacchi, 1999, Growth hormone in obesity, Int. J. Obes., 23, 260, 10.1038/sj.ijo.0800807

Schneider, 2006, Opposite associations of age-dependent insulin-like growth factor-I standard deviation scores with nutritional state in normal weight and obese subjects, Eur. J. Endocrinol., 154, 699, 10.1530/eje.1.02131

She, 2007, Disruption of BCATm in mice leads to increased energy expenditure associated with activation of a futile protein turnover cycle, Cell Metab., 6, 181, 10.1016/j.cmet.2007.08.003

Shoelson, 2006, Inflammation and insulin resistance, J. Clin. Invest., 116, 1793, 10.1172/JCI29069

Sowers, 2003, Obesity as a cardiovascular risk factor, Am. J. Med., 115, 37S, 10.1016/j.amjmed.2003.08.012

Summers, 2006, Ceramides in insulin resistance and lipotoxicity, Prog. Lipid Res., 45, 42, 10.1016/j.plipres.2005.11.002

Tischler, 1982, Does leucine, leucyl-tRNA, or some metabolite of leucine regulate protein synthesis and degradation in skeletal and cardiac muscle?, J. Biol. Chem., 257, 1613, 10.1016/S0021-9258(19)68081-6

Tremblay, 2005, Overactivation of S6 kinase 1 as a cause of human insulin resistance during increased amino acid availability, Diabetes, 54, 2674, 10.2337/diabetes.54.9.2674

Tremblay, 2007, Identification of IRS-1 Ser-1101 as a target of S6K1 in nutrient- and obesity-induced insulin resistance, Proc. Natl. Acad. Sci. USA, 104, 14056, 10.1073/pnas.0706517104

Tremblay, 2007, Role of dietary proteins and amino acids in the pathogenesis of insulin resistance, Annu. Rev. Nutr., 27, 293, 10.1146/annurev.nutr.25.050304.092545

Trujillo, 2006, Adipose tissue-derived factors: impact on health and disease, Endocr. Rev., 27, 762, 10.1210/er.2006-0033

Um, 2006, Nutrient overload, insulin resistance and ribosomal protein S6 kinase 1, D6K1, Cell Metab., 3, 393, 10.1016/j.cmet.2006.05.003

Wellen, 2005, Inflammation, stress, and diabetes, J. Clin. Invest., 115, 1111, 10.1172/JCI200525102

Wittchen, 2005, Cardiovascular risk factors in primary care patients: methods and baseline prevalence results from the DETECT program, Curr. Med. Res. Opin., 12, 619, 10.1185/030079905X38187

Wu, 2004, ENU mutagenesis identifies mice with mitochondrial branched-chain aminotransferase deficiency resembling human maple syrup urine disease, J. Clin. Invest., 113, 434, 10.1172/JCI19574

Zhang, 2007, Increasing dietary leucine intake reduces diet-induced obesity and improves glucose and cholesterol metabolism in mice via multimechanisms, Diabetes, 56, 1647, 10.2337/db07-0123