Do You Have a Faulty Fat Sensor?
Researchers have discovered that a faulty fat sensor may be the cause of obesity and liver disease in a significant portion of the world according to a recent study published in the journal Nature. The results of their findings are that not only does this offer a promising target for new drugs to treat obesity and metabolic disorders, but that it could also offer a genetic test to see if you have a faulty fat sensor.
Fatty acids are a necessity to maintaining good health. However, how the body monitors and manages these fatty acids makes all the difference in the world when it comes to whether you are obese or lean.
In the gut are fatty acid receptors that act as sensors for detecting the free fatty acids that float around in our bloodstream after a meal. Some fatty acid receptors are classified as belonging to a family of G-proteins that act as sensors for signaling a wide range of biochemical processes. One G-protein in particular that has been identified as an important part of our physiology that recognizes long chain unsaturated fatty acids, controls fat cell genesis and controls our appetite and food preferences is known as GPR-120.
When unsaturated fatty acids from food bind to GPR-120, hormones are released that suppress appetite and stimulates the pancreas to secrete insulin. At the same time, fat cells are stimulated to divide in order to create more fat cells for storing the additional fat to prevent fat accumulation in the liver and deposits on the arterial walls.
To better understand, how GPR-120 works, researchers from the School of Public Health at Imperial College London led by Professor Philippe Froguel, decided to investigate what happens with mice that carry a genetic defect that makes them deficient in GPR-120 fat sensing protein.
In the study, normal wild type (WT) mice and mice deficient in the GPR-120 fat sensing protein (GPR-120 deficient mice) were fed a normal diet (15% fat content) and were found to both have similar weight gain. Furthermore, fasting plasma glucose and insulin blood levels were similar in both types of mice.
When both types of mice were fed a high fat diet (60% fat content), both types became obese; however, the GPR-120 deficient mice became even more-so obese and weighed 10% more than the WT mice. In addition, the GPR-120 deficient mice showed higher levels of fasting plasma glucose and insulin than the WT mice did.
Dissection of the mice showed that the GPR-120 deficient mice had fewer, but significantly larger fat cells and had more fat stored around their internal organs and within their livers than did the WT mice. Blood chemistry of these mice showed that obesity-associated insulin resistance was also more severe in the GPR-120 deficient mice that were fed a high fat diet in comparison to the WT mice.
Genetic analysis revealed that RNA synthesis (the precursor of protein manufacture) in both types of mice differed by as many as over 100 genes in liver to liver comparisons. And, that insulin signaling related molecules were significantly decreased by the lack of GPR-120 in both adipose tissue and the livers in the GPR-120 deficient mice.
The relevance of these findings is that they follow the same patterns of obesity associated with type 2 diabetes and heart disease in humans.
To determine whether a similar correlation in results can be seen in humans, the researchers analyzed the gene for GPR-120 in 6,942 obese people and 7,654 controls. What they were looking for was to see whether there are differences in the DNA code for GPR-120 that can be linked to individuals who are obese.
What they found was that one mutation in particular in the gene sequence coding for GPR-120 renders the fat sensing protein dysfunctional and thereby increases an individual’s risk of obesity by 60 percent. Furthermore, the researchers believe that this mutation mimics the effect of a diet that lacks unsaturated omega-3 fatty acids.
"Being overweight is not always unhealthy if you can make more fat cells to store fat," said Professor Froguel. "Some people seem to be unable to do this, and instead they deposit fat around their internal organs, which is very unhealthy. Our study suggests that in both mice and humans, defects in GPR-120 combined with a high-fat diet greatly increase the risk of this unhealthy pattern of obesity. We think GPR-120 could be a useful target for new drugs to treat obesity and liver diseases."
While a new drug for treating GPR-120 deficient individuals is years away, what can be done relatively quickly is a simple gene test to let obese individuals know whether they possess a faulty fat sensor that may play a significant part of their obesity. The value to this bit of knowledge is that it would offer some explanation for the personal difficulty individuals find with weight loss and could be useful in helping nutritionists and dieticians create a personalized diet plan for some clients.
Image Source: Courtesy of MorgueFile
Reference: "Dysfunction of lipid sensor GPR120 leads to obesity in both mouse and human." A. Ichimura et al.; Nature, published online 19 February 2012. doi:10.1038/nature10798.