Fat on the Mind
A protein is shown to control appetite in adult mice, and may affect people too
Gaining weight might be in your head after all. Tufts researchers have found a protein expressed in the brain that appears to play a key role in inducing satiety in adult mice, and suggest that it might well be critical for humans, too.
Overeating is a weighty topic these days, given that one-third of the population in the United States is obese and another third is overweight, according to the Centers for Disease Control and Prevention. A primary factor in maintaining healthy weight is the amount of food consumed. Now Maribel Rios, an assistant professor of neuroscience at the Sackler School of Graduate Biomedical Sciences, and her colleagues have shown that a particular protein, called brain-derived neurotrophic factor (BDNF), is critical in mediating satiety in adult mice. It’s an especially relevant finding given that more than a quarter of Americans are thought to carry BDNF mutations.
In a recent article in the Journal of Neuroscience Rios reports that when the BDNF gene was deleted in two of the primary appetite-regulating regions of the brain, mice ate more and became significantly heavier than their unaffected counterparts. It had been known that mice missing BDNF as they develop overeat and develop obesity as young mice, but it was unclear if it affected satiety in adult animals.
Now Rios and her colleagues have established that BDNF acts as a satiety signal in the mature brain independent of its apparent action during development of the brain. They have also shown that BDNF synthesis in two areas of the brain—the ventromedial (VMH) and dorsomedial hypothalamus (DMH)—is required for normal energy balance in adult mice. “This important distinction might help define disease mechanisms and critical periods of intervention for the treatment and prevention of obesity disorders,” says Rios.
When directly administered to the brain, BDNF “is a fast-acting, signal-inducing neuronal activity within neural circuits involved in appetite control,” Rios says. It is apparently limited in scope, not affecting regulation of non-appetite-related behaviors.
The obesity exhibited by BDNF-depleted mice appears to arise solely from over-consumption. The affected mice went back to normal body weight when food access was limited, indicating that deletion of the BDNF gene doesn’t affect energy expenditure.
“Our results establish that BDNF plays a prominent and direct role in the regulation of energy balance in adult mice,” says Rios, whose research was supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases and National Institute of Mental Health. “It appears that this signaling pathway acts, at least partly, through short-term mechanisms and that BDNF synthesis in the VMH and DMH is required for suppression of appetite.
“This work brings us closer to elucidating the brain pathways that rely on BDNF to modulate food intake,” Rios says, while noting that additional studies are needed to further pinpoint the cellular and molecular targets of BDNF action. “The relevance of the BDNF signaling pathway in human disease is highlighted by the obesity exhibited by certain humans carrying mutations or abnormalities in the genes coding for BDNF or its receptor. This is bound to be an important area of obesity research as more than a quarter of the American population is estimated to carry mutations in the BDNF gene.”
This story ran in the February 2008 issue of the Tufts Journal.