USF Health researchers uncover a hidden brain region that helps regulate metabolism

Study identifies the first known function of an understudied brain region that helps coordinate how the body responds to cold temperatures and regulates metabolic health.

When the body's temperature falls, it adapts by burning more energy to generate heat and triggering appetite to replace the fuel used to stay warm.

While scientists have known about those responses for decades, precisely how the brain coordinates that process has remained unclear.

New research led by USF Health's Dr. Yong Xu uncovered new clues to that puzzle in a little-studied region of the brain.

In a study published today in Neuron, researchers working in non-human models identified a previously unknown brain circuit that turns a drop in temperature into a coordinated response regulating eating, heat production and energy use in the body.

The discovery represents the first known function of a previously underexamined brain region in the back part of the hypothalamus called the dorsal posterior periventricular hypothalamic nucleus, or dPVp, a region that has received little attention by researchers.

"We identified a very understudied brain region and then found the first function for that brain region," said Xu, professor in the Department of Psychiatry and Behavioral Neurosciences at the USF Health Morsani College of Medicine and director of the Center for Molecular Psychiatry. "The basic function of the dPVp is to sense temperature fluctuations and then coordinate a comprehensive set of behaviors or metabolic changes to deal with cold exposure."

The study shows that dPVp functions as a cold-response control center in the brain, becoming highly active when body temperatures drop and activating neurons that intensify the desire to eat and increase the body's ability to up its heat production.

To determine the region's function, researchers experimentally manipulated activity of cold-responsive neurons within the dPVp, revealing its central role in coordinating the body's behavioral and metabolic responses to cold exposure.

Activating dPVp neurons produced unexpected metabolic effects, Xu said, increasing the drive to consume more food while also burning more energy, helping prevent weight gain and improve glucose regulation.

The study also identified a biological "cold sensor" protein within dPVp neurons helping brain cells detect the cold and coordinate the body's response.

Known as KCNK2 or TREK-1, this cold sensor offers researchers a potential new target for developing drug therapies that could mimic the metabolic benefits associated with a response to cold exposure.

"One of the future directions is to use that as a drug target to try to develop highly selective inhibitors for KCNK2 as a future medicine," said Dr. Hailan Liu, faculty member in the USF Health Center for Molecular Psychiatry and first author on the study.

The findings could hold long-term implications for treating obesity, type 2 diabetes and other metabolic disorders. While many current approaches focus on reducing appetite, future treatments could instead target the newly identified pathway to improve metabolic function by helping the body burn and use more energy.

"If successful treatments were developed targeting the cold sensor, we wouldn't have to expose people to cold temperatures to achieve those benefits," Xu said. "One could maintain metabolic health without dieting."