Genetic Background of Fats reveals a majestic result

There are several efforts been made to investigate the association of fats in family background although several attempts well known to regulate by proper diet and exercise, but genetic insights may also help for proper prevention and treatment.
Harvard Medical Research investigators and MIT provides a majestic explanation behind the genetic association leading to obesity. The research was published in New England Journal of Medicine, reveals a major genetic circuit with new approach for obesity in patients.
Image Courtesy: Harvard Medical School

Earlier several attempts been made to identify how FTO gene associate with obesity. The risk for obesity behind these attempts was still vague to bring out the conclusive result. “Despite of investigating the FTO obesity region, no substantial expression differences were found between obesity-risk and non-risk individuals in brain or other tissue type, making it difficult to trace its mechanism of action,” said Manolis Kellis, professor of MIT’s CSAIL.
Researchers collected the adipose or fat tissue samples from patients with variant and also from non-variant control individuals; where they found distinct increased expressions of IRX3 and IRX5 genes by the risk variant. “We found a strong difference for both IRX3 and IRX5 genes in preadepocytes, revealing the target genes, cell type and developmental stage where the genetic variant acts, thus enabling us to begin dissecting its mechanism of action,” said Kellis.
To manipulate the exact role of these genes, the team inhibited the genes in the fat cells of mice. The result was majestic, since animals’ metabolism were increased and started losing weight although their physical activity and appetite were kept normal. “The results at the organism level were dramatic. These mice were 50 percent thinner than the control mice, and they did not gain any weight on a high-fat diet. Instead they dissipated more energy, even in their sleep, suggesting a dramatic shift in their global metabolism. Their circuitry underlying the FTO region functions like a master regulatory switch between energy storage and energy dissipation” said Melina Claussnitzer, an HMS instructor in medicine and an investigator in the Division of Gerontology at Beth Israel Deaconess and Hebrew Senior Life, a visiting professor at MIT’s Computer Science and artificial Intelligence Laboratory (CSAIL), and the member of Broad Institute.
The researchers then sought to connect the differences in metabolism and genetic differentiation between lean and obese people within FTO gene. They hypothesized that a single nucleotide variation from T to C in FTO gene may associate in obesity by repressing the conserved gene regulator ARID5B.
“Bidirectional genome editing of the casual nucleotide variant allowed us to demonstrate that a single nucleotide is responsible for flipping this metabolic switch between obese and lean individuals”, said Claussnitzer. She also added, “this is the first time that causality has been demonstrated for a genetic variant in a distal non-coding region, but we hope it will be first of many studies to come, now that genome editing is becoming broadly adopted”.
The story was adopted from the press release of Harvard Medical School.