Scientists engaged in the fight against obesity have long been aware that white fat cells are unhealthy because they store triglycerides and other harmful substances, while brown fat is desirable because it burns energy and protects against excessive weight gain. But efforts to understand how white fat becomes “beige” and takes on all the good characteristics of brown fat—and to translate that into antiobesity treatments—have largely failed.
Now researchers from the University of Michigan and American University believe they’ve uncovered a signaling pathway that prompts beige cells to burn energy. Surprisingly, they discovered that nicotine contributes to this process—a revelation that could explain why some smokers say the habit helps them lose weight.
The team zeroed in on a signaling pathway called CHRNA2. By monitoring the activity of more than 20 neurotransmitters in mice, they discovered that the pathway is active when the body is converting brown fat to energy to protect against cold—one of the key functions of this type of adipose tissue. When the researchers deactivated CHRNA2, the mice not only struggled to fend off the chills, they also gained weight, according to a statement.
When the researchers started measuring levels of the neurotransmitters in fat cells, they discovered that nicotinic acetylcholine was inducing CHRNA2 signaling. They believe therapies targeting the CHRNA2 signaling pathway could be effective in fighting obesity. Their research was published in the journal Nature Medicine.
“Until recently, we thought this pathway primarily existed in brain cells, the neuromuscular junction, and affected neuronal signaling, and we didn't know it was prevalent in certain fat cells," said co-author Alexander Zestos, a bioanalytical neurochemist at American University, in the statement. "It raises all sorts of new questions. Is it the density of the receptors that a person has, or is it the way the receptors are activated, that contributes to one's ability to gain or lose weight? What is the connection between smoking and weight loss or weight gain?"
The researchers also investigated mice engineered to lack the CHRNA2 protein, and discovered that when they were fed a high-fat diet, they had more weight gain and higher levels of insulin and blood glucose. Those are signals of diabetes risk, said researchers at the University of Michigan in a statement.
The potential to turn white fat beige has inspired other obesity researchers, too. A team at the Perelman School of Medicine at the University of Pennsylvania has been investigating a different signaling pathway that involves the proteins FLCN and mTOR, which they discovered work in tandem to prevent the browning of white fat. When they deleted the gene that makes FLCN in mice, they were able to prompt the beiging of white fat. They had previously achieved the same result in mice when they activated mTORC1 and mTORC2.
The nicotine connection is intriguing to Zestos and his co-authors, and they are currently searching for a compound that can target CHRNA2 signaling for weight loss and to prevent obesity, sans cigarettes, of course. They are also investigating other neurological chemicals that may activate beige fat.