New Data Published in Nature Medicine from Joslin Diabetes Center Demonstrates the Importance of Interrogating Human Biology

BOSTON, March 27, 2017 /PRNewswire/ -- BERG, a biopharmaceutical company uncovering health solutions through a data-driven, biological research approach, today announced that the company's Interrogative Biology® Platform contributed to the discovery of new data using a cold-induced model to promote thermogenesis and facilitate brown fat metabolism. Joslin Diabetes Center led the investigation with BERG providing its Interrogative Biology® platform for analysis of samples.  The findings were published in Nature Medicine (DOI number: 10.1038/nm.4297) on March 27, 2017.

Researchers at Joslin state in an announcement on the findings that, activated by cold, small amounts of brown fat in the body can burn calories to warm up a person. Brown fat can also help to lower insulin resistance and other conditions implicated in type 2 diabetes and obesity. Since the discovery in 2009 that brown fat can be active in adult humans, researchers around the world have worked to unveil ways to switch on this fat. Scientists at Joslin, guided by BERG's advanced lipids analysis, now have identified a new route to throw the switch.

The investigators have shown that a lipid (a fat-like substance) called 12,13-diHOME molecules that circulates in the blood signals brown fat cells in mice to fuel up with other lipids. In one experiment, obese mice given low levels of the molecule produced reduced levels of blood triglycerides—other forms of lipids that can increase risks for heart disease and diabetes in humans. Although the Joslin team hasn't shown that 12,13-diHOME also triggers brown fat activation in humans, the lipid could aid research by acting as a biomarker for the process, notes Yu-Hua Tseng, Ph.D., a Joslin principal investigator and senior author on the paper.

The researchers are now gathering more details on the molecular mechanisms by which 12,13-diHOME may affect brown fat activation. If the lipid does indeed assist in activating brown fat in humans, it may offer a route toward therapies, and the route may attract particular interest because we produce this substance naturally. "We would like to take our research from the bench to the bedside by engaging with clinical investigators here at Joslin," Tseng says.

The study began with a cohort of nine healthy human volunteers, taking blood samples first at normal room temperatures and then at temperatures cold enough to activate brown fat. Levels of 12,13-diHOME rose significantly among all the volunteers in the cold. Additionally, knowing that brown fat activity in humans decreases as obesity increases, the team measured circulating 12,13-diHOME in 55 people with a wide range of ages and body weights. The scientists found a negative correlation of 12,13-diHOME with measures of body mass index (BMI), insulin resistance, circulating triglycerides and liver enzymes that are related to fatty liver disease. In mice models, studies similarly showed that this lipid can activate fuel uptake into brown fat, and improve brown fat performance.