Professor Michael Cowley
Head - Department of Physiology
BSc (Hons) (Melbourne), PhD (Monash)
Pfizer Senior Research Fellow (2009-14)
Department of Physiology
Monash University VIC 3800
Room F280, Building 13F (Physiology) at Clayton Campus
Tel: +61 3 990 52526
Michael Cowley is a member of the Metabolic Neuroscience research group. Research within the Cowley lab began by studying the cellular and neural circuitry responses to signals of energy status: how the brain determines how much energy (fat) is stored in the body. We set out to map the pathways that are engaged by signals of energy state, and how these pathways relay information to the rest of the brain. Using this map of the melanocortin circuits in the hypothalamus (the region of the brain responsible for basic functions including thirst, hunger, the desire to reproduce and other essential processes) we were able to discover new signals within the body that regulate energy balance and describe how other known energy signals exert their effects on the brain.
Research in the lab now focuses on how these signals from the body lose ability to control our weight once the person is obese. We seek to determine how and why the brain becomes resistant to signals that are meant to convey that the body has sufficient stores of energy, and should start to burn more, and eat less.
A possible explanation for the recent increase in obesity relates to the very rewarding aspects of highly palatable foods, in other words why are sweet or fatty foods more "tasty" than other foods? Furthermore, why do we continue to engage in eating behavior that is obviously bad for us?
We wish to determine how the reward based pathways and homeostatic pathways interact, and how reward overrules homeostatic signals of satiety (the feeling that one can always squeeze in one more piece of chocolate cake…). We seek to better understand the structure of the neural pathways by which the reward and homeostatic circuits interact.
Selective leptin resistance and causes of metabolic syndrome
The major aim of this study is to determine if high leptin levels in the blood of obese mammals contributes to pathologically high blood pressure, increased heart rate, and diabetes by activating the sympathetic nervous system. Understanding the common cause of these conditions will potentially lead to improvement in patient care, and pave the way for new treatments for illnesses in obese humans.
Brain control of blood glucose levels
The major aim of this study is to determine the mechanisms of action of melanocyte stimulating hormone (α-MSH) effects on glucose homeostasis and how glucose sensing in POMC neurons (a specific group of neurons in the brain that detect blood sugar levels) of obese mice and monkeys could be restored. This project aims to contribute to the elucidation of an important mechanism in the basic control of glucose homeostasis, and highlighting a new drug development target.
Reward and obesity. Food; Too much of a good thing?
Recent Key Publications
1. SE Simonds, JT Pryor, E Ravussin, FL Greenway, R Dileone, AM Allen, J Bassi, JK Elmquist, JM Keogh, E Henning, MG Myers Jr, J Licinio, RD Brown, PJ Enriori, S O’Rahilly, SM Sternson, DC Spanswick, KL Grove, IS Farooqi, MA Cowley. Leptin mediates the increase in blood pressure associated with obesity. Cell. Dec 2014;159:1404-16
2. Wilson JL, Chen W, Dissen GA, Ojeda SR, Cowley MA, Garcia-Rudaz C, Enriori PJ. Excess of Nerve Growth Factor in the Ovary Causes a Polycystic Ovary-Like Syndrome in Mice, which Closely Resembles Both Reproductive and Metabolic Aspects of the Human Syndrome. Endocrinology. 2014 Sep 11
3. Secher A, Jelsing J, Baquero AF, Hecksher-Sørensen J, Cowley MA, Dalbøge LS, Hansen G, Grove KL, Pyke C, Raun K, Schäffer L, Tang-Christensen M, Verma S, Witgen BM, Vrang N, Knudsen LB. The arcuate nucleus mediates GLP-1 receptor agonist liraglutide-dependent weight loss. J Clin Invest. 2014 Sep 9. pii: 75276.
4. Litwak SA, Wilson JL, Chen W, Garcia-Rudaz C, Khaksari M, Cowley MA, Enriori PJ. Estradiol prevents fat accumulation and overcomes leptin resistance in female high fat diet mice. Endocrinology. 2014 Aug 22
5. Billes SK, Sinnayah P, Cowley MA. Naltrexone/bupropion for obesity: An investigational combination pharmacotherapy for weight loss. 2014. Pharmacol Res. 2014. 84C: 1-11.
6. Baquero AF, de Solis AJ, Lindsley SR, Kirigiti MA, Smith MS, Cowley MA, Zeltser LM, Grove KL. Developmental switch of leptin signaling in arcuate nucleus neurons. J Neurosci. 2014; 34:9982-94.
7. Jacobi JS, Coleman HA, Enriori PJ, Parkington HC, Li Q, Pereira A, Cowley MA, Clarke IJ. Paradoxical effect of gonadotropin-inhibiting hormone (GnIH) to negatively regulate neuropeptide Y neurons in mouse arcuate nucleus. 2013 J Neuroendocrinol. 12:1308-17
8. Lee SJ, Verma S, Simonds SE, Kirigiti MA, Kievit P, Lindsley SR, Loche A, Smith MS, Cowley MA, Grove KL. Leptin stimulates neuropeptide y and cocaine amphetamine-regulated transcript coexpressing neuronal activity in the dorsomedial hypothalamus in diet-induced obese mice. 2013. J Neurosci. 33:15306-17
9. P Kievit, H Halem, DL Marks, JZ Dong, MM. Glavas, P Sinnayah, L Pranger, MA. Cowley, KL. Grove, and MD Culler. 2013 Chronic treatment with a melanocortin 4 receptor agonist causes weight loss, reduces insulin resistance and improves cardiovascular function in diet induced obese Rhesus macaques. Diabetes. 62: 490-7
10. SK Billes, SE Simonds, & MA Cowley. Leptin reduces food intake via a dopamine D2 receptor dependent mechanism. 2012 Molecular Metabolism;1: 86-93. With accompanying editorial.
11. Chen W, Wilson JL, Khaksari M, Cowley MA, Enriori PJ. Abdominal fat analysed by Dxa scan reflects visceral body fat and improves the phenotype description and the assessment of metabolic risk in mice. Am J Physiol Endocrinol Metab. 2012. 303:E635-43.
12. Clarke SD, Clarke IJ, Rao A, Cowley MA, Henry BA. Sex differences in the metabolic effects of testosterone in sheep. Endocrinology. 2012. 153: 123-31.
13. MA Sabin, CG Magnussen, M Juonala, MA Cowley, JPH Shield. The role of pharmacotherapy in the prevention and treatment of paediatric metabolic syndrome – implications for long-term health. Pharmacological Research. 2012. 65: 397-401.
14. K Loh; A Fukushima; X Zhang; S Galic; D Briggs; PJ Enriori; S Simonds; F Weide; A Reichenbach; C Hauser; N A Sims; KK Bence; S Zhang; Z-Y Zhang; BB Kahn; BG Neel; ZB Andrews; MA Cowley; T Tiganis. Elevated hypothalamic TCPTP in obesity contributes to cellular leptin resistance. Cell Metabolism. 2011. 14: 684-99.
15. PJ Enriori, P Sinnayah, SE Simonds, CG Rudaz, MA Cowley. Leptin action in the dorsomedial hypothalamus increases sympathetic tone to brown adipose in spite of systemic leptin resistance. 2011. The Journal of Neuroscience. 31:12189-97.
16. Tamas L. Horvath, Beatrix Sarman, Cristina García-Cáceres, Pablo J. Enriori, Marya Shanabrough, Erzsebet Borok, Jesus Argente, Julie A. Chowen, Diego Perez-Tilve, Paul T. Pfluger, Hella S. Brönneke, Barry E. Levin, , Sabrina Diano Michael A. Cowley*and Matthias H. Tschöp*. Synaptic Input Organization of the Melanocortin System Predicts Diet-Induced Hypothalamic Reactive Gliosis and Obesity * Joint corresponding authors. 2010 Proc Natl Acad Sci U S A. 107:14875-80