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Other Joint Appointments

Faculty, Kellog School of Science and Technology

Research Focus

The United States is experiencing an epidemic of obesity. Abundant calorie-rich foods and reduced physical activity leads to weight gain and increased risk of developing insulin resistance and diseases of the metabolic syndrome. Determining the mechanisms involved in the homeostatic regulation of appetite and expenditure of energy is an important step in the development of new therapies against obesity and diabetes. The Butler lab has two areas of interest. We are investigating how the 24 rhythms of wakefulness and metabolism are regulated by nutrients. During periods of nutrient scarcity, organisms rapidly synchronize their circadian rhythm with nutrient intake. Our data suggests that the melanocortin-3 receptor (MC3R), a g-protein-coupled receptor expressed in the brain, is involved in this process. MC3R are regulated by neuropeptides released from neurons which respond to local and systemic signals of metabolic state and nutrient intake. Loss of MC3R function results in an impaired ability to anticipate nutrient intake, and results in a condition resembling diabetes and the metabolic syndrome observed with obesity. We are now investigating the function of MC3R-expressing neurons in the hypothalamus which may have a critical role in maintaining glucose homeostasis. Our second research focus is a novel hormone which we have called adropin. Adropin is a peptide hormone released by the liver in response to signals of metabolic state, and also appears to be regulated by dietary fat intake. Studies in the laboratory suggest that obesity is a state of adropin deficiency. We have observed that deletion of the gene encoding adropin results in a "pre-diabetic" condition. Moreover, adropin therapy has shown promise in preclinical studies, improving the metabolic syndrome associated with obesity. We are now examining the mechanisms involved in the regulation of metabolic homeostasis by adropin.

Education

B.Sc., (Zoology), University of Canterbury, Christchurch, New Zealand, 1990
Ph.D., University of Auckland, Auckland, New Zealand, 1995

Professional Experience

Postdoctoral training:
Fogarty International Fellow at the National Institute of Diabetes, Digestive and Kidney Diseases, NIH (1996-1997)
The Vollum Institute, Oregon Health & Science University (1998-2001).

Previous Faculty Appointments:
Assistant Professor (2001-2005); Associate Professor (2005-2009), The Pennington Biomedical Research Center, Louisiana State University System.

Awards & Professional Activities

Editorial boards
Endocrinology
Journal of Clinical Investigation (Consulting Editor)
Scientific Reports

Awards
Lilly Scientific Achievement Award from The Obesity Society (2008)
Junior Faculty Award from the American Diabetes Association (2004-2007)

Selected References

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. * corresponding authors.

Discussed by Pissios P and Maratos-Flier E - More Then Satiety: Central Serotonin Signaling And Glucose Homeostasis (News and Views). Cell Metabolism 2007 Nov; 6(5):345-347, and in Miller KJ and Azzara AV - An Old Dog Leans A New Trick: Regulation Of Peripheral Glucose Homeostasis By The Serotonin (5-HT)2C receptor. Molecular Interventions 2008 8:73-77, and in Crunkhorn S - Metabolic Disease: New Opportunity for Serotonin Receptor Agonists. Nature Reviews Drug Discovery
Faculty of 1000 - must read.

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.
Faculty of 1000 selection - recommended.

Begriche K, Lavasseur PR, Zhang J, Rossi J, Solt LA, Marks DL, Young B, Burris TP, Mynatt RL and Butler AA. Genetic dissection of the functions of the melanocortin-3 receptor, a seven-transmembrane G-protein coupled receptor, indicates roles for central and peripheral receptors in energy homeostasis. Journal of Biological Chemistry Nov 25, 286(47):40771-40781.

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.

 

Sutton GM, Centanni AV, Butler AA. Protein malnutrition during pregnancy in C57BL/6J mice results in offspring with altered circadian physiology before obesity. Endocrinology 2010 Apr;151(4):1570-80.

Discussed by Reyes TM and Simmons RA - Setting the “Clock”: Importance of Maternal Diet (Editorial). Endocrinology 2010 151(4), 1385-1386.

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.

 

Yang H, Youm YH, Vandanmagsar B, Rood J, Kumar KG, Butler AA, Dixit VD.Obesity accelerates thymic aging. Blood 2009 Oct 29;114(18):3803-12.

 

Perez-Tilve D, Hofmann SM, Basford J, Nogueiras R, Pfluger PT, Patterson JT, Grant E, Wilson-Perez HE, Granholm NA, Arnold M, Trevaskis JL, Butler AA, Davidson WS, Woods SC, Benoit SC, Sleeman MW, DiMarchi RD, Hui DY, Tschöp MH. Melanocortin signaling in the CNS directly regulates circulating cholesterol.Nat Neurosci. 2010 Jul;13(7):877-82.

Discussed by Yi-Chun Loraine Tung and Giles SH Yeo. Central melanocortin signaling regulates cholesterol  (News and Views). Nature Neuroscience 2010 Jul; 13(7), 779-780.
Faculty of 1000 selection - must read.

Links

Scripps Research Appoints Two New Faculty Members to the Department of Metabolism and Aging in Florida

Scripps researcher gets $1M from Novo Nordisk