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鈥檚 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鈥檚 uncovered new clues to that puzzle in a little-studied region of the brain.
In a study published today in , 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.
鈥淲e identified a very understudied brain region and then found the first function
for that brain region,鈥 said Xu, professor in the at the USF Health Morsani College of Medicine and director of the . "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.鈥
A fluorescent microscope image of brain tissue reveals cellular activity that is helping researchers better understand how the brain uses energy. (Image courtesy of Dr. Hailan Liu)
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鈥檚 ability to up its heat production.
To determine the region鈥檚 function, researchers experimentally manipulated activity
of cold-responsive neurons within the dPVp, revealing its central role in coordinating
the body鈥檚 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 鈥渃old sensor鈥 protein within dPVp neurons helping brain cells detect the cold and coordinate the body鈥檚 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.
鈥淚nstead of simply lowering food intake, this pathway may help the body use energy more efficiently."
Dr. Hailan Lu
鈥淥ne 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 , 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.
鈥淚f successful treatments were developed targeting the cold sensor, we wouldn鈥檛 have to expose people to cold temperatures to achieve those benefits,鈥 Xu said. 鈥淥ne could maintain metabolic health without dieting.鈥