Branched-chain amino acid levels are associated with improvement in insulin resistance with weight loss

被引:292
作者
Shah, S. H. [1 ,2 ,3 ]
Crosslin, D. R. [12 ]
Haynes, C. S. [2 ]
Nelson, S. [12 ]
Turer, C. B. [11 ]
Stevens, R. D. [3 ,8 ]
Muehlbauer, M. J. [3 ]
Wenner, B. R. [3 ]
Bain, J. R. [3 ]
Laferrere, B. [4 ]
Gorroochurn, P. [5 ]
Teixeira, J. [6 ]
Brantley, P. J. [7 ]
Stevens, V. J.
Hollis, J. F. [8 ]
Appel, L. J. [9 ]
Lien, L. F.
Batch, B.
Newgard, C. B. [3 ,10 ]
Svetkey, L. P. [3 ]
机构
[1] Duke Univ, Med Ctr, DUMC, Dept Med, Durham, NC 27710 USA
[2] Duke Univ, Med Ctr, Ctr Human Genet, Durham, NC 27710 USA
[3] Duke Univ, Sarah W Stedman Nutr & Metab Ctr, Durham, NC 27710 USA
[4] St Lukes Roosevelt Hosp, New York Obes Nutr Res Ctr, New York, NY USA
[5] Columbia Univ Coll Phys & Surg, Dept Biostat, New York, NY 10032 USA
[6] St Lukes Roosevelt Hosp, Div Minimally Invas Surg, New York, NY USA
[7] Pennington Biomed Res Ctr, Baton Rouge, LA USA
[8] Kaiser Permanente NW, Hlth Sci Programs, Ctr Hlth Res, Portland, OR USA
[9] Johns Hopkins Univ, Sch Med, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA
[10] Duke Univ, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA
[11] UT SW Med Ctr, Dept Med, Dallas, TX USA
[12] Univ Washington, Dept Biostat, Seattle, WA 98195 USA
基金
美国国家卫生研究院;
关键词
Amino acids; Biomarker; Insulin resistance; Metabolites; Weight loss; METABOLIC PROFILE; GLUCOSE; OBESE; RISK; SENSITIVITY; DISEASE; TISSUE; DIET; MEN;
D O I
10.1007/s00125-011-2356-5
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Insulin resistance (IR) improves with weight loss, but this response is heterogeneous. We hypothesised that metabolomic profiling would identify biomarkers predicting changes in IR with weight loss. Targeted mass spectrometry-based profiling of 60 metabolites, plus biochemical assays of NEFA, beta-hydroxybutyrate, ketones, insulin and glucose were performed in baseline and 6 month plasma samples from 500 participants who had lost a parts per thousand yen4 kg during Phase I of the Weight Loss Maintenance (WLM) trial. Homeostatic model assessment of insulin resistance (HOMA-IR) and change in HOMA-IR with weight loss (a dagger HOMA-IR) were calculated. Principal components analysis (PCA) and mixed models adjusted for race, sex, baseline weight, and amount of weight loss were used; findings were validated in an independent cohort of patients (n = 22). Mean weight loss was 8.67 +/- 4.28 kg; mean a dagger HOMA-IR was -0.80 +/- 1.73, range -28.9 to 4.82). Baseline PCA-derived factor 3 (branched chain amino acids [BCAAs] and associated catabolites) correlated with baseline HOMA-IR (r = 0.50, p < 0.0001) and independently associated with a dagger HOMA-IR (p < 0.0001). a dagger HOMA-IR increased in a linear fashion with increasing baseline factor 3 quartiles. Amount of weight loss was only modestly correlated with a dagger HOMA-IR (r = 0.24). These findings were validated in the independent cohort, with a factor composed of BCAAs and related metabolites predicting a dagger HOMA-IR (p = 0.007). A cluster of metabolites comprising BCAAs and related analytes predicts improvement in HOMA-IR independent of the amount of weight lost. These results may help identify individuals most likely to benefit from moderate weight loss and elucidate novel mechanisms of IR in obesity.
引用
收藏
页码:321 / 330
页数:10
相关论文
共 21 条
[1]   EXPLORATION OF SIMPLE INSULIN SENSITIVITY MEASURES DERIVED FROM FREQUENTLY SAMPLED INTRAVENOUS GLUCOSE-TOLERANCE (FSIGT) TESTS - THE INSULIN-RESISTANCE ATHEROSCLEROSIS STUDY [J].
ANDERSON, RL ;
HAMMAN, RF ;
SAVAGE, PJ ;
SAAD, MF ;
LAWS, A ;
KADES, WW ;
SANDS, RE ;
CEFALU, W .
AMERICAN JOURNAL OF EPIDEMIOLOGY, 1995, 142 (07) :724-732
[2]   Branched-chain amino acids and brain function [J].
Fernstrom, JD .
JOURNAL OF NUTRITION, 2005, 135 (06) :1539S-1546S
[3]  
Harlan L C, 1990, Epidemiology, V1, P224, DOI 10.1097/00001648-199005000-00008
[4]   Adipose Tissue Branched Chain Amino Acid (BCAA) Metabolism Modulates Circulating BCAA Levels [J].
Herman, Mark A. ;
She, Pengxiang ;
Peroni, Odile D. ;
Lynch, Christopher J. ;
Kahn, Barbara B. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2010, 285 (15) :11348-11356
[5]   Multi-tissue, selective PPARγ modulation of insulin sensitivity and metabolic pathways in obese rats [J].
Hsiao, Gene ;
Chapman, Justin ;
Ofrecio, Jachelle M. ;
Wilkes, Jason ;
Resnik, Jamie L. ;
Thapar, Divya ;
Subramaniam, Shankar ;
Sears, Dorothy D. .
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, 2011, 300 (01) :E164-E174
[6]   Relationships Between Circulating Metabolic Intermediates and Insulin Action in Overweight to Obese, Inactive Men and Women [J].
Huffman, Kim M. ;
Shah, Svati H. ;
Stevens, Robert D. ;
Bain, James R. ;
Muehlbauer, Michael ;
Slentz, Cris A. ;
Tanner, Charles J. ;
Kuchibhatla, Maragatha ;
Houmard, Joseph A. ;
Newgard, Christopher B. ;
Kraus, William E. .
DIABETES CARE, 2009, 32 (09) :1678-1683
[7]  
Knowler William C, 2002, N Engl J Med, V346, P393, DOI 10.1056/NEJMoa012512
[8]   Effect of weight loss by gastric bypass surgery versus hypocaloric diet on glucose and incretin levels in patients with type 2 diabetes [J].
Laferrere, Blandine ;
Teixeira, Julio ;
McGinty, James ;
Tran, Hao ;
Egger, Joseph R. ;
Colarusso, Antonia ;
Kovack, Betty ;
Bawa, Baani ;
Koshy, Ninan ;
Lee, Hongchan ;
Yapp, Kimberly ;
Olivan, Blanca .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2008, 93 (07) :2479-2485
[9]   Differential Metabolic Impact of Gastric Bypass Surgery Versus Dietary Intervention in Obese Diabetic Subjects Despite Identical Weight Loss [J].
Laferrere, Blandine ;
Reilly, David ;
Arias, Sara ;
Swerdlow, Nicholas ;
Gorroochurn, Prakash ;
Bawa, Baani ;
Bose, Mousumi ;
Teixeira, Julio ;
Stevens, Robert D. ;
Wenner, Brett R. ;
Bain, James R. ;
Muehlbauer, Michael J. ;
Haqq, Andrea ;
Lien, Lillian ;
Shah, Svati H. ;
Svetkey, Laura P. ;
Newgard, Christopher B. .
SCIENCE TRANSLATIONAL MEDICINE, 2011, 3 (80)
[10]   HOMEOSTASIS MODEL ASSESSMENT - INSULIN RESISTANCE AND BETA-CELL FUNCTION FROM FASTING PLASMA-GLUCOSE AND INSULIN CONCENTRATIONS IN MAN [J].
MATTHEWS, DR ;
HOSKER, JP ;
RUDENSKI, AS ;
NAYLOR, BA ;
TREACHER, DF ;
TURNER, RC .
DIABETOLOGIA, 1985, 28 (07) :412-419