Andrew A. Butler, Ph.D.
Pharmacological and Physiological Science
Ph.D., University of Auckland, Auckland, New Zealand (1995)
Diabetes Branch, National Institutes of Diabetes & Digestive & Kidney Diseases, National Institutes of Health, Bethesda, MD (1995-1998)
Vollum Institute, Oregon Health & Science University, Portland, OR (1998-2001)
Neural “nutrient sensing networks” control ingestive behaviors and metabolism to maintain metabolic homeostasis and a healthy body weight. The central nervous melanocortin system is a critical component of this network. Mutations that impair the activity of this system cause a hyperphagic obesity syndrome in humans, suggesting that it may be a target for developing treatment for obesity and associated metabolic diseases. Our group uses genetically modified mice to investigate the role of melanocortin receptors in maintaining metabolic homeostasis. We are mainly interested in the melanocortin-3 receptor (MC3Rs), a poorly understood component of the central nervous melanocortin system. Our results suggest MC3Rs play an essential role in adapting ingestive behaviors and metabolism to nutrient scarcity.
During our investigations of melanocortin receptor deficient mice, we identified a new peptide hormone (adropin) that is involved in metabolic homeostasis. Plasma levels of adropin are regulated by food intake and dietary macronutrients. Our data suggests adropin plays a role in regulating fuel selection (fats or glucose). Significantly, low plasma levels of adropin in humans may be a risk factor for the metabolic diseases with insulin resistance as a defining feature that are associated with obesity. This novel hormone may therefore be a promising lead in the development of new therapies for type 2 diabetes.
St-Onge MP, Shechter A, Shlisky J, Tam CS, Gao S, Ravussin E, Butler AA. Fasting plasma adropin concentrations correlate with fat consumption in human females. Obesity (Silver Spring). 2014 Apr;22(4):1056-63.
Girardet C, Butler AA. Neural melanocortin receptors in obesity and related metabolic disorders. Biochim Biophys Acta. 2014 Mar;1842(3):482-94.
Butler AA, Tam CS, Stanhope KL, Wolfe BM, Ali MR, O'Keeffe M, St-Onge MP, Ravussin E, Havel PJ. Low circulating adropin concentrations with obesity and aging correlate with risk factors for metabolic disease and increase after gastric bypass surgery in humans. J Clin Endocrinol Metab. 2012 Oct;97(10):3783-91.
Begriche K, Levasseur PR, Zhang J, Rossi J, Skorupa D, Solt LA, Young B, Burris TP, Marks DL, Mynatt RL, Butler AA. Genetic dissection of the functions of the melanocortin-3 receptor, a seven-transmembrane G-protein-coupled receptor, suggests roles for central and peripheral receptors in energy homeostasis. J Biol Chem. 2011 Nov 25;286(47):40771-81.
Butler AA, Kozak LP. A recurring problem with the analysis of energy expenditure in genetic models expressing lean and obese phenotypes. Diabetes. 2010 Feb;59(2):323-9.
Sutton GM, Begriche K, Kumar KG, Gimble JM, Perez-Tilve D, Nogueiras R, McMillan RP, Hulver MW, Tschöp MH, Butler AA. Central nervous system melanocortin-3 receptors are required for synchronizing metabolism during entrainment to restricted feeding during the light cycle. FASEB J. 2010 Mar;24(3):862-72
Kumar KG, Trevaskis JL, Lam DD, Sutton GM, Koza RA, Chouljenko VN, Kousoulas KG, Rogers PM, Kesterson RA, Thearle M, Ferrante AW Jr, Mynatt RL, Burris TP, Dong JZ, Halem HA, Culler MD, Heisler LK, Stephens JM, Butler AA. Identification of adropin as a secreted factor linking dietary macronutrient intake with energy homeostasis and lipid metabolism. Cell Metab. 2008 Dec;8(6):468-81.
Sutton GM, Perez-Tilve D, Nogueiras R, Fang J, Kim JK, Cone RD, Gimble JM, Tschöp MH, Butler AA. The melanocortin-3 receptor is required for entrainment to meal intake. J Neurosci. 2008 Nov 26;28(48):12946-55.
Zhou L*, Sutton GM*, Rochford JJ, Semple RK, Lam DD, Oksanen LJ, Thornton-Jones ZD, Clifton PG, Yueh CY, Evans ML, McCrimmon RJ, Elmquist JK*, Butler AA*, Heisler LK*. Serotonin 2C receptor agonists improve type 2 diabetes via melanocortin-4 receptor signaling pathways. Cell Metab. 2007 Nov;6(5):398-405. * equal contributors.
Sutton GM, Trevaskis JL, Hulver MW, McMillan RP, Markward NJ, Babin MJ, Meyer EA, Butler AA. Diet-genotype interactions in the development of the obese, insulin-resistant phenotype of C57BL/6J mice lacking melanocortin-3 or -4 receptors. Endocrinology. 2006 May;147(5):2183-96.
Honors and Awards
Junior Faculty Award, American Diabetes Association
Lilly Scientific Achievement Award, The Obesity Society
Professional Organizations and Associations
American Diabetes Association
The Endocrine Society
Journal of Clinical Investigation; Diabetes, Biochemical Journal