Brown adipose tissue is activated by the cold to release anti-inflammatory substances.
More than 40% of adult Americans are obese, a complicated condition that increases the risk of diabetes, heart disease and various cancers. By creating low-grade chronic inflammation and building up immune cells in insulin-sensitive tissues, obesity is a contributing factor to other health problems. Scientists believe that reversing or “resolving” this chronic inflammation could slow the rise of obesity-related diseases such as diabetes and perhaps make it easier to lose weight.
Researchers from Brigham and Women’s Hospital and the Joslin Diabetes Center found that in diet-induced obese mice, exposure to cold temperatures improved insulin sensitivity and glucose tolerance, while resolving obesity-induced inflammation. Their findings were reported in a new paper published in Nature Metabolism.
The research team also found that the mechanism relied on brown adipose tissue, commonly referred to as “good fat,” releasing a naturally occurring molecule called Maresin 2 in response to cold stimulation. Brown adipose tissue is known as an active endocrine organ because it secretes molecules that communicate with other tissues and regulate metabolism. It also aids in the release of stored energy and may promote weight loss and metabolic health.
“Extensive evidence indicates that obesity and metabolic syndrome are linked to chronic inflammation leading to systemic insulin resistance, so interrupting inflammation in obesity could offer promising therapies for obesity-related diseases,” said co-corresponding author Yu-Hua Tseng, Ph.D. ., a senior researcher in the section on integrative physiology and metabolism at the Joslin Diabetes Center and professor of medicine at Harvard Medical School.
“We found that exposure to cold reduced inflammation and improved metabolism in obesity, at least in part mediated by brown adipose tissue activation. These findings suggest a previously unrecognized function of brown adipose tissue in promoting the resolution of inflammation in obesity. .”
In two previous experiments, Tseng and colleagues found that brown fat can be activated by exposure to cold to create certain lipid mediators that regulate nutrient metabolism. In the current study, the researchers identified a new role for a lipid mediator produced from brown fat to resolve inflammation.
In the current study, the researchers created a mouse model that, when fed a standard high-fat, Western diet, develops obesity.
When the animals were exposed to a cold environment (about 40 degrees[{” attribute=””>Fahrenheit), the researchers observed that the animals’ insulin sensitivity and glucose metabolism improved and their body weight decreased, compared to control animals maintained at a thermoneutral zone – the environmental temperature where the body does not need to produce heat for maintaining its core body temperature.
What’s more, the scientists also noticed a profound improvement in inflammation, as measured by reduced levels of a major inflammatory marker.
“We found that brown fat produces Maresin 2, which resolves inflammation systemically and in the liver,” said co-corresponding author Matthew Spite, Ph.D., a lead investigator at Brigham and Women’s Hospital and Associate Professor of Anesthesia at Harvard Medical School. “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.”
Moreover, these findings also suggest that Maresin 2 could have clinical applications as a therapy for patients with obesity, metabolic disease, or other diseases linked to chronic inflammation; however, the molecule itself breaks down quickly in the body. Tseng and colleagues seek a more stable chemical analog for clinical use.
The team notes a shortcut to improved metabolic health may already exist. Multiple human studies conducted at Joslin and elsewhere show that exposure to mildly cold temperatures (50 to 55 degrees Fahrenheit) has been shown to be sufficient to activate brown adipose tissue and improve metabolism, though the mechanisms are not well understood.
Reference: “Brown adipose tissue-derived MaR2 contributes to cold-induced resolution of inflammation” by Satoru Sugimoto, Hebe Agustina Mena, Brian E. Sansbury, Shio Kobayashi, Tadataka Tsuji, Chih-Hao Wang, Xuanzhi Yin, Tian Lian Huang, Joji Kusuyama, Sean D. Kodani, Justin Darcy, Gerson Profeta, Nayara Pereira, Rudolph E. Tanzi, Can Zhang, Thomas Serwold, Efi Kokkotou, Laurie J. Goodyear, Aaron M. Cypess, Luiz Osório Leiria, Matthew Spite, and Yu-Hua Tseng, 27 June 2022, Nature Metabolism.
DOI: 10.1038/s42255-022-00590-0
This work was supported in part by US National Institutes of Health (NIH) grants (R01DK122808, R01DK077097, R01DK102898, R01HL106173, R01DK099511, R01DK112283, P30DK0368360) and by US Army Medical Research grant W81XWH-17-1-0428; the Manpei Suzuki Diabetes Foundation in Japan; grant 2019/20554-7 from The São Paulo Research Foundation, FAPESP; an American Diabetes Association post-doctoral fellowship (1-16-PDF-063); the Sao Paulo Research Foundation (FAPESP) grants 2017/02684 and 2019/26008-4.
Spite and Tseng are inventors of a pending provisional patent application related to Maresin 2 and metabolic therapeutics.