UCSF researchers discover brain cell's new role in controlling food intake

Members of the Koliwad lab at UC San Francisco’s Saunders Court on Thursday, November 20, 2014. Pictured from left are: Megan Robblee, Suneil Koliwad, Diana Alba and Martin Valdearcos Contreras (Photo: Kathleen Jay/UCSF)

UCSF researchers discover brain cell's new role in controlling food intake

Diabetes researchers focus on regulation of energy balance in the brain

BY KATHLEEN JAY

Diabetes Center at UCSF

This week, a novel study led by Diabetes Center investigator Suneil Koliwad, PhD, MD, identifies a new role for specific cells within the brain in controlling food intake.

Koliwad’s lab has found that these cells, called microglia, instruct brain circuits to promote food intake, particularly in situations when the consumption of saturated fat is excessive.

The study, entitled “Microglia Dictate the Impact of Saturated Fat Consumption on Hypothalamic Inflammation and Neuronal Function," was published online in the journal Cell Reports.

“For a while, it has been known that obesity can cause a form of low-grade inflammation that is linked to problems such as type 2 diabetes and heart disease,” Koliwad said. “Until recently, research on this type of inflammation was centered on tissues such as fat, muscle, liver and the pancreas – the organ responsible for producing insulin.

“However, obesity also produces inflammation in the hypothalamus, a region of the brain that controls appetite, energy balance and body weight. Our work has identified that microglia really orchestrate this type of brain inflammation by responding to high levels of saturated fat in the diet. They then dictate the impact of this inflammation on food intake,” Koliwad, who is also a practicing endocrinologist, added.

Martin Valdearcos Contreras, PhD, a member of Koliwad’s lab and first author on the paper, discovered by studying mice that saturated fats enter the brain and build up in the hypothalamus when consumed in large amounts. Microglia specifically sense this build-up and stimulate an inflammatory process, changing the function of nerve cells that control food intake.

By targeting microglia, Valdearcos could control both the inflammatory effects of saturated fats in the brain, and reduce daily food intake in the mice without producing any obvious ill effects.

“Microglia have classically been thought of as responding to infectious and other insults,” Valdearcos said. “Our team has done a great job of showing that these cells can also sense dietary factors, such as particular fats, and instruct nerve cells accordingly.”

“In this way, microglia don’t just protect against dire threats, they also determine day-to-day functions, such as the brain’s ability to cope with dietary shifts,” Koliwad said. “We now know that the instructive capacity of microglia is a determinant of metabolic function, something that we may target to unlock new ways to control obesity and type 2 diabetes.”

“Our ultimate goal is to find safe and effective ways to control microglia, and to prevent long-term metabolic disorders which can ultimately cause the onset of diabetes,” Koliwad said.

Koliwad, whose research area of focus is lipid metabolism and inflammation, and his Diabetes Center colleague Allison Xu, PhD, who concentrates on better understanding the regulation of energy balance in the brain, together received a UCSF Diabetes Family Fund grant, which supported the project’s conception and the team’s collaborative research on this study.

“Suneil and Allison’s study is the first of its kind to shed light on how diet-induced inflammation in the brain can lead to adverse consequences, such as dysregulation of body weight and metabolism,” Matthias Hebrok, PhD, director of the Diabetes Center, said. “The Diabetes Center is thrilled with their research and important discovery.”

For more information, visit http://diabetes.ucsf.edu.

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