Brain-Cell ‘Antenna’ May be Key to Understanding Obesity

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UC San Francisco researchers have discovered that the brain’s ability to regulate body weight depends on a novel form of signaling in the brain’s “hunger circuit” via antenna-like structures on neurons called primary cilia. 

Primary cilia are distinct from motile cilia, the finger-like projections that act as a sort of cellular conveyer belt, with functions such as removing debris from the lungs and windpipe. Immotile primary cilia were once thought to be vestigial, like a cellular appendix, but in the past decade, research at UCSF and elsewhere has revealed that these structures play a key role in many forms of hormonal signaling in the body. 

Christian Vaisse, MD, PhDNow the new UCSF study – published Jan. 8 in Nature Genetics – shows that primary cilia also play a crucial role in signaling within the brain. Neuroscientists are accustomed to thinking of brain signaling in terms of direct chemical or electrical communication among neurons at sites called synapses, but the new findings reveal that chemical signaling at primary cilia may also play an important, and previously overlooked role. In addition, the findings suggest potential new therapeutic approaches to the growing global obesity epidemic, the researchers say. 

“We’re building a unified understanding of the human genetics of obesity,” said senior author Christian Vaisse, MD, PhD, a professor in the Diabetes Center at UCSF and a member of the UCSF Institute for Human Genetics. “Until recently, many obesity researchers had barely heard of primary cilia, but that’s going to change.”

Key Signaling Proteins in Brain’s Hunger Circuit

The modern epidemic of obesity is driven largely by environmental factors, including access to essentially unlimited sources of ready calories paired with increasingly sedentary lifestyles. But not everyone exposed to the same unhealthy conditions becomes overweight. Studies have estimated that genetics contribute between 40 and 70 percent to people’s inclination toward unhealthy weight gain.

Since the 1990 …

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