The brain represents the master coordinator of appetite and energy expenditure, employing interwoven neurological circuits to continually appraise and respond to changes in energy state.
Our research aims to discover and characterise these brain circuits using cutting edge technology with the objective of locating points within the pathway that are amenable to manipulation with manmade (drug) or natural (hormone) substances.
We also examine the impact of diet and body weight on circuit rewiring and mechanisms restore appropriate system connectivity and activity.
The ultimate aim of our research is to identify new treatments for obesity and type 2 diabetes.
We aim to elucidate the neuroendocrinology of energy homeostasis and neural influences on peripheral metabolism, in order to define novel therapeutic targets for obesity and type 2 diabetes.
There is significant genetic and pharmacological evidence that central melanocortin pathways, mostly through melanocortin-4 receptors, are critical in the regulation of neuroendocrine and behavioural parameters associated with energy balance/type 2 diabetes.
However, relatively little is known about the downstream pathways involved. We are adopting complementary neuroanatomical, pharmacological, genetic, physiological, and behavioural approaches to investigate such brain circuitry.
Specifically, our data suggest that the central serotonin system modulates melanocortin pathways, and we are currently exploring the expression of different serotonin receptors on melanocortin-containing cell bodies, and their differential modulation of effects on key nuclei in the hypothalamus and brainstem.
5-HT2C receptor agonist anorectic efficacy potentiated by 5-HT1B receptor agonist coapplication: an effect mediated via increased proportion of pro-opiomelanocortin neurons activated. Doslikova B, Garfield AS, Shaw J, Evans ML, Burdakov D, Billups B, Heisler LK.J Neurosci. 2013 Jun 5;33(23):9800-4.
Unraveling the brain regulation of appetite: lessons from genetics. Yeo GS, Heisler LK. Nat Neurosci. 2012 Oct;15(10):1343-9.
Neurochemical characterization of body weight-regulating leptin receptor neurons in the nucleus of the solitary tract. Garfield AS, Patterson C, Skora S, Gribble FM, Reimann F, Evans ML, Myers MG Jr, Heisler LK. Endocrinology. 2012 Oct;153(10):4600-7.
Brain glucose sensors play a significant role in the regulation of pancreatic glucose-stimulated insulin secretion. Osundiji MA, Lam DD, Shaw J, Yueh CY, Markkula SP, Hurst P, Colliva C, Roda A, Heisler LK, Evans ML. Diabetes. 2012 Feb;61(2):321-8.
Setting the tone: reactive oxygen species and the control of appetitive melanocortin neurons.Rochford JJ, Myers MG Jr, Heisler LK. Cell Metab. 2011 Nov 2;14(5):573-4. doi: 10.1016/j.cmet.2011.10.004.
Leptin does not directly affect CNS serotonin neurons to influence appetite.Lam DD, Leinninger GM, Louis GW, Garfield AS, Marston OJ, Leshan RL, Scheller EL, Christensen L, Donato J Jr, Xia J, Evans ML, Elias C, Dalley JW, Burdakov DI, Myers MG Jr, Heisler LK. Cell Metab. 2011 May 4;13(5):584-91