Home Other Sections Medical News Brain Gene Rap1 as Potential Drug Target for Obesity

Brain Gene Rap1 as Potential Drug Target for Obesity

119

Brain Gene Rap1 as Potential Drug Target for ObesityScientists from Baylor College of Medicine, the National Institutes of Health and Virginia Tech Carilion Research Institute have determined a new mechanism (Rap1 gene) inside the mouse brain that regulates obesity. The new study, which appears in the journal Cell Reports, suggests that this new mechanism can potentially be focused to treat weight problems.

According to the senior author Dr. Makoto Fukuda, assistant professor of pediatrics at Baylor and the USDA/ARS Children’s Nutrition Research Center at Baylor and Texas Children’s Hospital, It’s well known that the brain is involved in the development of obesity, but how a high-fat diet changes the brain so it triggers the accumulation of body fat is still unclear.

Fukuda and associates studied the mouse Rap1 gene, that’s expressed in many tissues, consisting of the brain where it’s involved in functions along with memory and learning. Little was recognised, however, of the role brain Rap1 plays in energy balance.

To explore the function brain gene plays in a mouse model, the scientists selectively deleted the Rap1 gene in a collection of neurons in the hypothalamus, a vicinity of the brain that is concerned in regulating entire-body metabolism.

The scientists had two groups of mice. In one group, the mice had been genetically engineered to lack the Rap1 gene, at the same time as the control group had a functional Rap 1 gene. Then, the scientists fed the mice in both groups with a high-fat eating regimen in which 60 percent of the energy came from fats. As anticipated, the mice with the Rap1 gene received weight, however, in evaluation, the mice that lacked Rap 1 had markedly decreased body weight and less body fats. Apparently, whilst each groups of mice were fed a normal diet, both confirmed comparable weights and body fats.

The Rap1 Gene

The scientists then looked nearer at why the mice lacking the Rap1 gene had not gained weight despite consuming a high-fats diet. Fukuda remarked, We observed that the mice lacking Rap1 were not more physically active. However, they ate less and burned more body fat than mice with Rap1. These observations were associated with the hypothalamus producing more of a hormone that reduces appetite, called POMC, and less of hormones that stimulate appetite, called NPY and AgRP. Those mice also had lower ranges of blood glucose and insulin than controls.

The scientists also were inquisitive about studying whether or not leptin modified in mice missing brain gene. Leptin, the ‘satiety hormone’ produced by fatty tissue, allows changes in body weight by inhibiting the urge for food. Overweight humans however do not reply to leptin’s indicators of satiety, and the blood stages of leptin are higher than those in non-overweight human beings. Leptin resistance is a trademark of human weight problems.

Mice that lacked Rap1 and ate an excessive-fats diet, then again, did not increase leptin resistance; they were capable of responding to leptin, and this turned into the hormone’s decrease blood levels.

Fukuda and co-workers also tested the impact of inhibiting Rap1 with medicines rather than deleting the gene on mice on a high-fat food regimen. The scientists inhibited brain gene action with inhibitor ESI-05. Fukuda remarked, When we administered ESI-05 to obese mice, we restored their sensitivity to leptin to a level similar to that in mice eating a normal diet. The mice ate less and lost weight. This new mechanism involving Rap1 in the brain may represent a potential therapeutic target for treating human obesity in the future

The scientists have proven a new mechanism by which the brain can affect the development of obesity by means of eating a high-fat food regimen. Ingesting a high-fats weight loss program results in adjustments inside the brain that increase Rap1 activity, which in turn leads to a decreased sensitivity to leptin, and this sets the body on a direction to weight problems.