Fat-burning molecule recruits neighboring cells in fight against obesity
Over the past decade or so we've seen research illuminate the important differences between the various types of fat in the human body. Part of this effort has focused on ways we might be able to turn bad fat into good fat to tackle obesity, and a new study has brought a new molecule into the mix, which the authors were able to demonstrate can be targeted with treatments to prevent weight gain in mice on high-fat diets.
Led by scientists at the University of Bonn, the research centers on the important differences between white fat and brown fat, and the way the body promotes one type over the other. While white fat is where the body stores excess energy in the form of beer bellies or love handles, brown fat burns lipids and glucose to generate body heat. This keeps us warm in cold temperatures and positions brown fat as the more desirable of the two forms.
"Nowadays, however, we're toasty warm even in winter," explains study author Dr. Alexander Pfeifer. "So our body's own furnaces are hardly needed anymore."
Further, lifestyles involving high-energy Western diets and little exercise compromise the wellbeing of brown fat cells in the body. These factors cause their function to deteriorate and the cells to eventually die off. Cell death elsewhere in the body induces the release of specific patterns of metabolites, so the scientists set out to explore this phenomenon in brown fat specifically.
"It is known that dying cells release a mix of messenger molecules that influence the function of their neighbors," explains study author Dr. Birte Niemann. "We wanted to know if this mechanism also exists in brown fat."
The team's experiments involved subjecting brown fat cells to severe stress to trigger their death. The scientists found that these cells secrete a molecule called purine inosine in large amounts, which in turn stimulates energy expenditure in neighboring, healthy brown fat cells. Mice on high-fat diets treated with inosine remained leaner than control mice and were protected from diabetes, and also experienced conversion of brown fat into white.
The scientists traced these effects to a protein in the cell membrane that transports inosine into the cell, which lowers the concentration outside the cell and in turn tempers the molecule's positive effects on energy expenditure. Around two to four percent of people suffer genetic variations that dampen the activity of this inosine transporter, and by studying these effects through genetic analysis of 900 subjects, the scientists uncovered some useful insights.
"Our colleagues at the University of Leipzig have genetically analyzed 900 individuals," Pfeifer explained. "Those subjects with the less active transporter were significantly leaner on average."
The scientists also took a drug developed to treat coagulation disorder that happens to inhibit the inosine transporter and gave it to mice, which saw them burn more energy as a result. This raises the prospect that drugs that target this mechanism could be deployed as treatments for obesity, though further research is needed to ascertain the safety and effectiveness of the approach.
"However, further studies in humans are needed to clarify the pharmacological potential of this mechanism," Pfeifer said. "But the available therapies are not effective enough at the moment. We therefore desperately need medications to normalize energy balance in obese patients."
The research was published in the journal Nature.
Source: University of Bonn
Please keep comments to less than 150 words. No abusive material or spam will be published.