Examining how endogenous cannabinoids regulate body weight

Researchers from the Warren Center for Neuroscience Drug Discovery have discovered how endogenous cannabinoids, those made by the body, modulate the "feeding cells" in the brain to regulate body weight. This study, led by Dr Masoud Ghamari-Langroudi, research assistant professor of molecular physiology and biophysics, research assistant professor of pharmacology and faculty affiliate, expands on his previous work involving Melanocortin 4 (MC4) receptors, which are crucial in regulating energy homeostasis, the balance of energy intake and expenditure in the body.

MC4 receptors respond to cannabinoid molecules, whether they are naturally in the body or from drugs such as cannabis. His lab used a variety of techniques, including behavioural studies, gene expression analysis, hormone assays and electrophysiology techniques, to map the brain circuits associated with cannabinoids and eating behaviour. The findings were featured in the paper, ‘Endogenous cannabinoids are required for MC4R-mediated control of energy homeostasis,’ published in the Proceedings of the National Academy of Sciences.


"We describe here how endogenous cannabinoids produced in the hypothalamus - a brain region important in homeostasis - can 'fine tune' the activity of the MC4 receptor feeding cells," explained Ghamari-Langroudi. "There has been a sharp increase in obesity and anorexia in recent years. We hope our research will offer an understanding of how feeding behaviour is regulated, which can also be an avenue to develop therapeutics."


MC4 receptors are implicated in a variety of disordered eating behaviours, including obesity and anorexia, making the Food and Drug Administration particularly interested in targeting them as a therapeutic tactic against associated disorders. The drugs that have been developed so far have adverse effects, including high blood pressure, according to Ghamari-Langroudi.


"This novel finding of regulation of MC4R neurons could potentially provide therapeutic tools to target energy homeostasis without the unwanted effects observed by current MC4R targeting drugs," he said.


Ghamari-Langroudi and his lab plan to continue this research to obtain an even clearer map of the neural circuits described in this study. They also hope to eventually find additional potential targets within this circuitry to understand and treat disordered eating.


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