Scientists at Joslin Diabetes Center have shown that a lipid called 12,13-diHOME 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. Although the Joslin team has not 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.
The research, ‘The cold-induced lipokine 12,13-diHOME promotes fatty acid transport into brown adipose tissue’, was published in the journal Nature Medicine, and lead by Dr Matthew Lynes, a Joslin postdoctoral researcher and lead author on a paper. They 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.
“After we identified this lipid in the human cohort, we used it to treat mice,” said Lynes. “We showed that it indeed can activate fuel uptake into brown fat, and improve brown fat performance.”
In other mice experiments, the Joslin team also demonstrated that 12,13-diHOME increases in the circulation of animals exposed to cold. Mice treated with 12,13-diHOME were able to better tolerate cold exposure. Still other tests demonstrated that the lipid is produced by brown fat cells exposed to cold.
Additionally, knowing that brown fat activity in humans decreases as obesity increases, the Joslin 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 BMI, insulin resistance, circulating triglycerides and circulating liver enzymes that are related to fatty liver disease.
The researchers now are 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.
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