Cold temperatures induce anti-inflammatory molecule that counters obesity
Researchers continue to unravel the complex role inflammation plays in obesity, and the influence it has on downstream effects such as insulin resistance, glucose control and diabetes risk. A new study has added important new insights in this space, demonstrating how cold temperatures can stimulate the release of a molecule that reverses this type of inflammation and reduces body weight in mice, laying the groundwork for novel therapeutics that induce similar effects in humans.
Led by scientists at Joslin Diabetes Center and Brigham and Women's Hospital, the study sought to further our understanding of the ways low-grade, chronic inflammation can lead to obesity-related health problems. Previous studies had shown that cold exposure can improve insulin sensitivity in both humans and rodents, and also that it can generate lipid mediators of inflammation in what's known as brown fat.
Brown fat is distinct from white fat (the type that stores excess energy and gives rise to beer bellies and love handles) in that it burns lipids and glucose to generate body heat to keep us warm. In this sense, brown fat is considered a "good" fat, and for this reason finds itself at the center of much obesity research aimed at converting one into the other to help address excess body weight and obesity-related health issues.
This new study involved mice fed a typical high-fat Western diet to make them obese. The animals were then exposed to cold environments with temperatures of around 40 °F (4.4 °C), and the scientists found that their sensitivity to insulin increased and their metabolism of glucose improved. Their body weight also decreased compared to control mice kept at neutral temperatures, and critically, the scientists found significant reductions in inflammation. The investigations revealed that these effects were dependent on the production of a naturally occurring molecule in brown fat called Maresin 2.
"We found that brown fat produces Maresin 2, which resolves inflammation systemically and in the liver," said co-corresponding author Matthew Spite. "These findings suggest a previously unrecognized function of brown adipose tissue in promoting the resolution of inflammation in obesity via the production of this important lipid mediator."
The discovery joins other interesting findings around the way fat behaves in response to different temperatures, such as a 2020 study showing how high-intensity interval training in the cold can boost fat-burning compared to training at neutral temperatures. While Maresin 2 itself breaks down too quickly in the body to be directly converted into a drug, the scientists are now searching for more stable chemical analogs that could be put to use to tackle the chronic inflammation associated with obesity.
"Extensive evidence indicates that obesity and metabolic syndrome are linked with chronic inflammation that leads to systemic insulin resistance, so interrupting inflammation in obesity could offer promising therapies for obesity-related disease," said co-corresponding author Yu-Hua Tseng.
The research was published in the journal Nature Metabolism.