Scientists have discovered a previously undocumented group of immune cells that interact with the nervous system to play a key role in obesity. They suggest that the breakthrough may lead to new targets for obesity treatments.
The researchers - led by Ana Domingos, Ph.D., from the Instituto Gulbenkian de Ciência in Portugal - describe the new immune cells, which they call sympathetic neuron-associated macrophages (SAMs), in a new paper published in the journal Nature Medicine.
Overweight and obesity pose major health risks because they raise the likelihood of developing type 2 diabetes, heart and circulation diseases, cancer, and other chronic diseases.
The worldwide epidemic of obesity and the health problems associated with it has increased scientific research into the underlying biology of the condition.
Macrophages and fat breakdown
In their study paper, Dr. Domingos and colleagues describe an area of research that is debating how a link between the immune system and the nervous system might affect fat breakdown.
Previous studies have suggested that macrophages that are active in obesity-related inflammation in fat tissue could be involved.
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However, the mechanisms linking the action of macrophages to the nervous system and fat breakdown have not been studied in depth.
In previous work, Dr. Domingos' team had discovered that fat, or "adipose tissue," has a supply of nerves made up of sympathetic nerve cells, or neurons, that release the neurotransmitter norepinephrine to trigger the breakdown of fat.
In the new study, they found that SAMs interact with, and influence the triggering of, the neurons that release the norepinephrine that triggers fat breakdown.
The team also discovered that SAMs dispose of norepinephrine and that obese mice have a much higher quantity of SAMs attached to neurons in fat tissue than lean mice.
The team suggests that this shows that SAMs play a key role in obesity by reducing norepinephrine in fat tissue, which, in turn, blocks the process of fat reduction.
Blocking protein boosted fat breakdown
Further investigations using genetically engineered mice uncovered more details about the underlying molecular mechanisms.
These showed that SAMs alone have a protein called Slc6a2 that latches onto norepinephrine. As far as they know, the researchers say that SAMs are the only type of immune cell that have this transporter protein.
The team also discovered that blocking this transporter protein in SAMs increased fat breakdown, energy use, and weight loss in the mice.
Finally, by analyzing nervous system samples from humans, the researchers discovered that we have an equivalent mechanism for clearing out norepinephrine.
Dr. Domingos suggests that targeting the norepinephrine transporter in SAMs may offer a way to overcome the "noxious off-target effects of several known drugs that block this molecular target."
"Overall, our results identify SAMs as a potential new molecular and cellular target for obesity therapy."