A switch that occurs in neurons within the hypothalamus could explain the body’s tendency to maintain higher, undesirable weight levels, rather than an ideal weight, according to new research. The switch involves receptors that trigger or inhibit the release of the orexin A peptide, which stimulates the appetite, among other behaviors.
The team of American and Italian neuroscientists found that in normal-weight mice, activation of this receptor decreases orexin A release. In obese mice, activation of this receptor stimulates orexin A release.
“The striking finding is that you have a massive shift of receptors from one set of nerve endings impinging on these neurons to another set,” says Ken Mackie, M.D., professor in the department of psychological and brain sciences in the College of Arts and Sciences at Indiana University Bloomington. “Before, activating this receptor inhibited the secretion of orexin; now it promotes it. This identifies potential targets where an intervention could influence obesity.” Dr. Mackie’s team at the Gill Center for Biomolecular Science at IU Bloomington collaborates with Vincenzo Di Marzo, Ph.D.’s team at the Institute of Biomolecular Chemistry in Pozzuoli, Italy.
Both teams study the endocannabinoid system, which is composed of receptors and signaling chemicals that occur naturally in the brain and have similarities to the active ingredients in marijuana. This neurochemical system is involved in a variety of physiological processes including appetite, pain, mood, stress responses, and memory.
You can read the abstract at NIH: Obesity-driven synaptic remodeling affects endocannabinoid control of orexinergic neurons