Physiology Staff

Physiology home About News and Events Department of Physiology Seminars Publications Staff Profiles Location Prospective Students Undergraduate courses Research in Physiology Entrance Requirements Studying Physiology Careers in Physiology Honours in Physiology

Professor Michael Cowley
Professorial Fellow - Department of Physiology
BSc (Hons) (Melbourne), PhD (Monash)

Director of modi (Monash Obesity and Diabetes Institute)
Pfizer Senior Research Fellow (2009-14)

Address
Department of Physiology
Monash University VIC 3800
Australia

Located
Room F232, Building 13F (Physiology) at Clayton Campus

Tel: +61 3 990 52526
Fax: +61 3 990 52547
Email: michael.cowley@monash.edu

Research Interests

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.

Current Projects

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

Glavas MM, Kirigiti MA, Xiao XQ, Enriori PJ, Fisher SK, Evans AE, Grayson BE, Cowley MA, Smith MS, Grove KL. Early overnutrition results in early-onset arcuate leptin resistance and increased sensitivity to high-fat diet. Endocrinology. 2010 Apr;151(4):1598-610.

Greenway FL, Dunayevich E, Tollefson G, Erickson J, Guttadauria M, Fujioka K, Cowley MA; for the NB-201 Study Group. Comparison of Combined Bupropion and Naltrexone Therapy for Obesity with Monotherapy and Placebo. J Clin Endocrinol Metab. 2009 Oct 21

Roth CL, Enriori PJ, Gebhardt U, Hinney A, Müller HL, Hebebrand J, Reinehr T, Cowley MA. Changes of peripheral alpha-melanocyte-stimulating hormone in childhood obesity. Metabolism. 2009 Sep 17

A Stefanidis, ANA Verty, AM Allen, NC Owens, MA Cowley and BJ Oldfield. The Role of Thermogenesis in Antipsychotic Drug-induced Weight Gain. (2009). Obesity (Silver Spring). 17:16-24.

J Xu, MA Kirigiti, MA Cowley, KL Grove, and MS Smith. (2009). Suppression of basal spontaneous GnRH neuronal activity during lactation: role of inhibitory effects of NPY. Endocrinology. 150:333-40.

FL Greenway, MJ Whitehouse, M Guttadauria, JWAnderson, RL Atkinson, K Fujioka, KM Gadde, AK Gupta, PO’Neil, D Schumacher, D Smith, E Dunayevich, GD Tollefson, E Weber & MA Cowley. 2009 Rational Design of a Combination Medication for the Treatment of Obesity. Obesity 17:30-9.

P Sinnayah, EE Jobst, JA Rathner, AD Caldera-Siu, LTonelli-Lemos, AJ Eusterbrock, PJ Enriori, EN Pothos, KL Grove & MA Cowley. (2008). Feeding induced by cannabinoids is mediated independently of the melanocortin system. PLoS One. May 21;3 (5):e2202.

Q Wu, MP Howell, MA Cowley, RD Palmiter. (2008).  Starvation after AgRP neuron ablation is independent of melanocortin signaling. Proc Natl Acad Sci U S A. 105 (7):2687-92.

NM Wallingford, P Sinnayah, FP Bymaster, KM Gadde, RK Krishnan, AA McKinney, RP. Landbloom, GD Tollefson and MA Cowley. (2008). Zonisamide prevents olanzapine-associated hyperphagia, weight gain, and elevated blood glucose in rats. Neuropsychopharmacology. In Press.

LE Parton, CP Ye, R Coppari, PJ Enriori, B Choi, C-Y Zhang, C Xu, CR Vianna, N Balthasar, CE. Lee, JK. Elmquist, MA. Cowley*, BB. Lowell. (2007). Glucose-sensing by POMC neurons regulates glucose homeostasis and is impaired in obesity. Nature. 449: 228-32.

SK Billes & MA Cowley. (2007). Catecholamine reuptake inhibition causes weight loss by increasing locomotor activity and thermogenesis. Neuropsychopharmacology.  33: 1287-1297.

JM Scarlett, EE Jobst, PJ Enriori, DD Bowe, AK Batra, WF Grant, MA Cowley* & DL Marks. (2007). Regulation of central melanocortin signaling by interleukin-1b.Endocrinology. 148:4217-25.

PJ Enriori, AE Evans, P Sinnayah, EE Jobst, L Tonelli-Lemos, SK Billes, MM Glavas, BE Grayson, M Perello, EA Nillni, KL Grove, MA Cowley. (2007). Diet-induced obesity causes severe but reversible leptin resistance in arcuate melanocortin neurons. Cell Metab. 5:181-194.

FL Greenway, CK Martin, AK Gupta, S Cruickshank, J Whitehouse, L DeYoung, K Kamdar, MK Caruso, AT Roberts, M England, K Dumas, BJ Laidlaw, B Rogers & MA Cowley. (2007). Using intranasal lidocaine to reduce food intake. International Journal of Obesity 31, 858-863.

SK Billes & MA Cowley. (2007). Inhibition of dopamine and norepinephrine reuptake produces additive effects on energy balance in lean and obese mice. Neuropsychopharmacology 32, 822-834.

FH Koegler, PJ Enriori, SK Billes, DL Takahashi, MS Martin, RL Clark, AE Evans, KL Grove, JL Cameron & MA Cowley.  (2005).  PYY(3-36) inhibits morning, but not evening, food intake and decreases body weight in rhesus macaques. Diabetes, 54: 3198-204.

MA Cowley, S Diano, M Tschöp, N Pronchuk, CJ Strasburger, M Bidlingmaier, M Esterman, RG Smith, ML Heiman, LM Garia-Segura, ES Nilni, P Mendez, MJ Low, WF Colmers, RD Cone,  TL Horvath. (2003). The distribution and mechanism of action of ghrelin in the CNS demonstrates a novel hypothalamic circuit regulating energy homeostasiss.  Neuron 37:649-61.

MA Cowley, RL Batterham, CJ Small, H Herzog, MA Cohen, CL Dakin, AM Wren, AE Brynes, MJ Low, MA Ghatei, RD Cone, SR Bloom. (2002).  Gut hormone PYY(3-36) physiologically inhibits food intake. Nature 418:650-4.

LK Heisler, MA Cowley, LH Tecott, W Fan, MJ Low, JL Smart, M Rubinstein, JB Tatro, H Holstege, CE Lee, RD Cone, JK Elmquist. (2002)  Fenfluramine activates central melanocortin pathways. Science 297:609-611.

MA Cowley, JL Smart, M Rubinstein, MG Cerdán, TL Horvath, S Diano, RD Cone, MJ Low.(2001). Leptin activates anorexigenic POMC neurons through a neural network in arcuate nucleus Nature 411:480-4.