While it is well-known that weight gain results from an imbalance between what we eat and
our energy expenditure, not so obvious is the role the nervous system plays in controlling
energy balance. Scientists have shed light on the question.
“Our new study has identified novel populations of nerve cells that regulate appetite, thermos enesis and
physical activity,” said TSRI Professor Baoji Xu, who led the research. “We think these neurons could be
targets for drug development.”
The findings were published by the journal Cell Metabolism online ahead of print on June 11.
In the new study, Xu and his colleagues examined several groups of neurons that express a substance
called “brain-derived neurotrophic factor” (BDNF) within a small brain region called the paraventricular
BDNF is an extremely important protein in the brain and is involved in a number of functions. It has been
shown that deleting the BDNF gene causes significant problems, among them, dramatically increased
appetite (hyperphagia) and severe obesity.
The new study shows that deleting the BDNF gene also impairs thermogenesis — the ability of cells to
burn fat to produce heat. The study further reveals two distinct types of BDNF neurons — those that
control appetite or satiety and those that control thermogenesis. Not only do these two groups play
different biological roles, they are located in two separate sections of the paraventricular hypothalamus
This “geographical” split raises some interesting questions. “We don’t yet know what the distinctive
placement means to the control of body weight, nor do we know if these two clusters of neurons
communicate with each other as yet,” said Juanji An, the first author of the study and a member of the
Xu lab. “But given the fact that mice and humans with mutations in the BDNF gene or its receptor
develop severe obesity, a better understanding of the mechanism underlying the effect BDNF has on
body weight could provide great insights into the regulation of energy balance.”
Xu is also hopeful about the potential of BDNF as a drug target. “Our findings suggest that activation of
each of these two populations of neurons should powerfully suppress appetite or promote energy
expenditure,” he said. However, he cautions that because BDNF’s functions are so widespread, a good
drug candidate would need to closely target only BDNF-expressing neurons in the paraventricular
hypothalamus, thus limiting potential side effects.
In addition to Xu and An, other authors of the study, “Discrete BDNF Neurons in the Paraventricular
Hypothalamus Control Feeding and Energy Expenditure,” include Guey-Ying Liao and Clint E. Kinney of
TSRI, and Niaz Sahibzada of the Georgetown University Medical Center.
The above post is reprinted from materials provided by Scrips Research Institute. Note: Materials
may be edited for content and length.