Recently discovered genetic switch might be a potential cure for obesity
Aug 27, 2015 · by · no comments
Obesity is undoubtedly one of the biggest health challenges of modern age. The World Health Organization (WHO) predicts that overweight and obesity may soon replace commonpublic health issues including under nutrition and infectious diseases as the most significant cause of poor health. In past, researchers have described how obesity increases the likelihood of various diseases, particularly cardiovascular diseases, diabetes, sleep problems, cancer, and osteoarthritis. But now, there may be a new approach to prevent and even cure obesity. The credit goes to a breakthrough study published in the New England Journal of Medicine which was led by researchers at MIT and Harvard Medical School. The study have unraveled a new genetic pathways that control human metabolism by stimulating fat cells to store fat or burn it away as heat.
Obesity has traditionally been known to be caused by an imbalance between the amount of calories we eat and how much we consume, but this description ignores the contribution of genetics to an individual’s metabolism, says author ManolisKellis, a professor of computer science and a fellow of Computer Science and Artificial Intelligence Laboratory (CSAIL) at MIT and of the Broad Institute.
The strongest genetic association with obesity resides in a region known as “FTO gene,” which is known to be the center piece of intense research since its discovery in 2007. Nonetheless, previous studies have failed to find any mechanism to explain how differences in FTO gene can cause obesity. On the other hand, many studies tried to find a link between FTO gene andbrain circuits that control our eating habits or tendency to exercise, says Melina Claussnitzer, a visiting professor at CSAIL and medicine instructor at BID Medical Center and Harvard Medical School. Our results indicated that the obesity-associated FTO gene acts predominantly in adipocyte progenitor cells, Claussnitzeradded.A progenitor cell is a biological cell that is like a stem cell but more specific than a stem cell and is programmed to differentiate into its target cell.
To study the effects of genetic differences in these precursor adipocytes (fat cell), the researchers gathered adipose samples from healthy Europeans. They found that samples taken from the people at higher risk of obesityhave an activated FTO gene on their adipocytes, which turned on two distant genes, IRX3 and IRX5.Follow-up experiments showed that IRX3 and IRX5 genes act as master controllers of thermogenesis. It is aprocess by which fat cells dissipate dietary calories as heat, instead of storing it as fat. Usually, thermogenesis is triggered by sympathetic responses, exercise, diet, or exposure to cold.
Based on their findings, the scientistsanticipated that a genetic difference of only one of four nucleotides is associated with obesity. In high risk individuals, a thymine (T) was found to be replaced by a cytosine (C) nucleobase. Thismutation disrupts suppression of the control FTO gene and turns on IRX3 and IRX5 genes. As a result thermogenesis shuts down which leads to lipid accumulation and eventually obesity.By editing a single nucleotide position, the researchers could switch between lean and obese genetics in human precursor adipocytes. Switching back the cytosine base to thymine turns off IRX3 and IRX5 genes, which restore thermogenesis back to normal.The experiment on lab animalsled to dramatic body changes in energy balance, resulting not only in a reduction of body weight and all major fat stores, but also in permanent resistance to any high-fat dietary intakes.
To conclude the study, Kallis explained that with these newly discovered genetic changes, we could easily switch between fat storage and fat dissipation as energy, providing new hope tocure obesity.The research is in its initial phases and experts are currently establishing alliances with other academics and industry to translate their findings into obesity therapeutics. Their approach also provides a model for future research to explore the links of other disease-associated genes.
Source: MIT News
Helen Knight (August 19, 2015)