Drive To Overeat Triggered By Key Shift In The Brain
April 30, 2013

Cellular Change In The Hypothalamus Linked To Obesity

redOrbit Staff & Wire Reports - Your Universe Online

New research published in the Proceedings of the National Academy of Sciences Early Edition this week has identified a cellular change in the brain that has been linked to obesity.

In the study, a team of American and Italian neuroscientists joined forces to identify a switch that occurs in neurons located within the hypothalamus. This switch, they explain in a statement, “involves receptors that trigger or inhibit the release of the orexin A peptide, which stimulates the appetite, among other behaviors.”

They studied both normal-weight and obese mice. In normal mice, activation of the receptor decreases the release of orexin A, while in overweight mice, activation of the receptor stimulates release of the peptide. They claim that their findings could explain why the body tends not to maintain desirable weight levels, and could also identify potential new treatment targets for overweight patients.

“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,” Ken Mackie, professor in the Indiana University Bloomington Department of Psychological and Brain Sciences, said in a statement.

“Before, activating this receptor inhibited the secretion of orexin; now it promotes it. This identifies potential targets where an intervention could influence obesity,” he added. The work was part of a long-term collaboration between IU Bloomington and the Institute of Biomolecular Chemistry in Pozzuoli, Italy.

Both Mackie and his Indiana colleagues and the Italian team, which is led by Vincenzo Di Marzo, study the endocannabinoid system, which is comprised of the receptors and signaling chemicals which occur naturally in a person´s brain and are comparable to the active ingredients in marijuana. This neurochemical system, they say, are involved in pain, stress, appetite, and several other physiological processes.

The consumption of food is controlled in part by the hypothalamus and regulated by the endocannabinoid system, as well as several other neurochemical systems. According to Mackie, a new theory is that obesity effectively resets the network, making it so that it matches up with the maintenance of a person´s current weight, not their ideal weight.

As a result, an overweight individual has trouble keeping weight off because his or her brain triggers a signal to encourage eating more in an attempt to return to their heavier weight.

“Using mice, this study found that in obesity, CB1 cannabinoid receptors become enriched on the nerve terminals that normally inhibit orexin neuron activity, and the orexin neurons produce more of the endocannabinoids to activate these receptors,” the Bloomington-based university explained. “Activating these CB1 receptors decreases inhibition of the orexin neurons, increasing orexin A release and food consumption.”

“The researchers conducted several experiments with mice to understand how this change takes place,” they added. “They uncovered a role of leptin, a key hormone made by fat cells that influences metabolism, hunger and food consumption. Obesity causes leptin levels to be chronically high, making brain cells less sensitive to its actions, which contributes to the molecular switch that leads to the overproduction of orexin.”