Obesity is a growing problem around the world, no pun intended. Lean models grace the covers of health and fitness magazines, but they certainly do not represent the average reader. Heaviness once was a symbol of wealth and prosperity. Today, extra weight is associated with laziness, a lack of concern for one’s self, and in some cases poverty. We now seem to be in an eternal struggle to permanently eliminate excess fat.
Weight gain is commonly a symptom of overeating combined with a lack of exercise. In some unfortunate cases, failure in an area of the brain known as the hypothalamus can lead to excess body fat. The hypothalamus responds to hormone signals from the body to regulate both hunger and metabolism. If the hypothalamus is compromised, abnormal eating behaviors as well as inadequate metabolic processing can occur. Due to the current obesity “epidemic,” there is an increased interest in understanding neural control over the factors that affect weight gain.
The ability to test predictions about brain activity and obesity in humans is limited due to the ethical problems generated by inhibiting human neural function. Clearly, another model is needed to study the association of brain performance and fat processing.
Both humans and fruit flies share many aspects of fat storage and metabolism. Each organism absorbs fat in the intestine, contains dedicated tissue for fat storage, and synthesizes new fat in specialized cells. In fact, many of the molecular factors required for each of these biological events is conserved between humans and flies.
Last week, a group of scientists lead by Dr. Bader Al-Anzi of the California Institute of Technology reported one more similarity: as in humans, there are neurons in the fruit fly brain that control eating behavior and fat metabolism.
Al-Anzi’s team adapted a chemical test, called rapid thin layer chromatography, to measure the total fat levels in the adult fruit fly body. The group screened the fat levels in hundreds of flies, each fly containing a brain with different combinations of neurons inhibited. His team successfully identified two populations of neurons, called c673a and fruitless, that when inhibited generated fat flies. Interestingly, when these same neurons were hyper-activated, the flies were significantly leaner!
Upon closer examination, Al-Anzi and colleagues determined that the inhibition of c673a neurons provoked increased food intake and decreased fat metabolism, while the silencing of fruitless neurons only affected metabolic processes. In each case, the group was able to reverse the obesity by removing the neural inhibition.
The authors suggest that a signal with information about energy stores in the body, perhaps from the fat cells, is detected by the c673a and fruitless neurons in the brain. These particular target neurons then process the received information to control feeding behaviors and fat metabolism.
With the identity of fat-regulating neurons established in fruit flies, future research can now utilize this model system to determine how neural networks link together to process signals from the body and to identify the genetic components involved in the development and function of such a tightly regulated system. Because many of the molecules that control fat processing in the body are conserved between flies and humans, insights gained from experiments on the fruit fly brain may one day reveal interesting and useful information about our own noggins.
The bottom line: That old childish taunt “fat-head” might not be so far from the truth.
Reference: Al-Anzi et al. “Obesity-Blocking neurons in Drosophila” Neuron 63, 329–341, August 13, 2009 DOI 10.1016/j.neuron.2009.07.021