New types of neurons controlling feeding
Substantial progress has been made in identifying the possible signals for initiating and terminating the appetitive aspects of feeding behavior in vertebrates. Strong evidence now implicates ATP (or an ATP-like molecule) and a fall in glucose in initiati
Scientists studying the molecular mechanisms regulating food intake and body weight have recently identified two types of neurons in the brain that control feeding in mice. Moreover, they have identified potential targets in these neurons for the treatment of obesity.
The study, led by Dr. Jeffrey Friedman at The Rockefeller University, is described in the prestigious international journal Cell.
More than 20 years ago, the lab of Dr. Friedman identified an important hormone that regulates body weight -- leptin. Since then, his lab has been engaged in elucidating the molecular basis of the actions of leptin and its receptors.
Leptin, a protein produced by fat cells, decreases a person's appetite. It circulates in the blood and goes to the brain. Leptin receptors are expressed in many tissues in the body, including the hypothalamus in the brain. Leptin acts on leptin receptors in the hypothalamus to regulate appetite, food intake and body weight.
Leptin resistance, meaning being resistant to the hormone's effects, is a major cause of obesity in humans. However, only some obese patients benefit from leptin therapy.
Food intake is also controlled by other brain regions besides hypothalamus. In this work, using a cutting edge whole-brain imaging technique called iDISCO+ and several other methods, Dr. Friedman's team examined the activity of different brain areas in fed and fasted mice. These analyses revealed that subsets of neurons in the dorsal raphe nucleus (DRN) in the brain were activated in fasted or re-feeding mice, suggesting that the DRN might regulate feeding.
Previous evidence has implicated the DRN in the control of food intake but which neurons are responsible for this effect remains unknown.
For this work, Dr. Friedman's team showed that changes in energy balance activated neurons in the DRN that expressed vesicular transporters for GABA or glutamate. Manipulation of these neurons controlled the feeding, activity and body weight of leptin-deficient obese mice. Finally, the study identified molecules in these neurons that might be targeted to control energy balance.
According to the researchers, manipulating specific DRN neurons may be a new strategy to combat obesity and this strategy is independent of leptin action.
