14 DAY TRIAL // Western world is experiencing an obesity pandemics, triggered by high-calorie content food, overeating and sedentariness. A new research published in "The Journal of Neuroscience" and carried on by a team led by Dr. Maribel Rios, an assistant professor of neuroscience at the Sackler School of Graduate Biomedical Sciences, at Tufts University School of Medicine in Boston, has found for the first time a chemical involved in overeating: a protein named brain-derived neurotrophic factor (BDNF).
Mice engineered to lack Bdnf gene in two of the primary appetite-regulating brain areas ate more and turned overweight. "We knew that the global lack of BDNF and/or its receptor during development leads to overeating and obesity in young mice. However, it remained unclear and controversial whether BDNF mediated satiety in adult animals. Our recent findings demonstrate that BDNF synthesis in the ventromedial (VMH) and dorsomedial hypothalamus (DMH) is required for normal energy balance. We were able to establish that BDNF acts as a satiety signal in the mature brain independently from its putative actions during development of the brain. This important distinction might help define disease mechanisms and critical periods of intervention for the treatment and prevention of obesity disorders", said Rios.
The engineered mice turned obese just through overeating.
"Normal body weight was restored in mutant mice when food access was limited to that of normal mice, indicating that deletion of the Bdnf gene in the VMH and DMH does not affect the expenditure side of the energy balance equation", said Rios.
The team also determined the levels of BDNF synthesis connected to nutritional status.
"The amount of BDNF mRNA produced decreased during periods of fasting. However, when the mice were exposed to glucose, a macronutrient, we observed a rapid, but transient, increase in the expression of BDNF and its receptor. These changes occurred specifically in the VMH, which is known to be involved in the regulation of food intake", said first author Thaddeus Unger.
Thus, glucose has a direct impact in the brain, controlling the hunger sensation.
"Direct administration of BDNF into the brain also led to an immediate increase in the levels of an early-response gene and marker of nerve-cell activation in both the VMH and the DMH. These results suggest that BDNF is a fast-acting signal inducing neuronal activity within neural circuits involved in appetite control. Mice with site-specific perturbation of BDNF expression did not exhibit behavioral abnormalities typically observed in mice with global deletion of the Bdnf gene throughout the brain, such as hyperaggression, depressive-like behavior, and hyperactivity. The absence of these behaviors suggests that BDNF expression in the VMH and DMH is not required for regulation of non-appetite-related behaviors. 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", said Rios.
"This work brings us closer to elucidating the brain pathways that rely on BDNF to modulate food intake. 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 on the American population has been estimated to carry mutations in the Bdnf gene", she added.