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NIH awards Scripps Research $2.35M to study new treatment for obesity

September 16, 2015

Brown fat, which has been identified in healthy humans, serves as a kind of molecular mammalian furnace, generating heat by burning large numbers of calories in creatures like newborn babies (and rodents) that lack the ability to shiver effectively to keep warm. The fat gets its name because it is loaded with mitochondria, the cell's energy plant, which contains iron and gives the fat its red-brown tint. Mitochondria use nutrients to produce energy for the cell.

The grant, Griffin said, is built on several key discoveries the team has made over the last few years. One is the initial discovery of PRDM16, a protein capable of determining whether certain types of immature cells will develop into brown fat cells. The protein works in tandem with another protein and together they act as the catalyst to the development of brown fat in different cell types. One aim of the funded research program will be to investigate regulation of whole body energy homeostasis and to isolate and characterize a type of brown fat cell in white fat tissues with substantial heat-producing capacity. This will be combined with the synthesis and evaluation of small molecules that can regulate PRDM16's activity.

A second discovery by the research team, which was published earlier this year in the journal Nature, was a novel signaling pathway trigged by phosphorylation of PPARg, the molecular target of the antidiabetic drugs called thiazolidenediones or TZDs. The research team is building on this discovery and is in the process of generating proof-of-concept compounds that modulate only this pathway. These compounds, in addition to being antidiabetic, have the potential to enhance brown fat leading to weight loss.

Source: Scripps Research Institute