Brown adipose tissue is activated by cold to release anti-inflammatory compounds.
Over 40% of American adults suffer from obesity, a complex disease that increases the risk of diabetes, heart disease, and several types of cancer. By creating low-grade chronic inflammation and the accumulation of immune cells in insulin-sensitive tissues, obesity is one factor that may contribute to other health problems. Scientists believe that reversing or “solving” this chronic inflammation could delay the onset of obesity-related diseases, such as diabetes, and possibly facilitate weight loss.
Researchers at the Brigham and Women’s Hospital and 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 are presented in a new article that was published in: Nature’s metabolism.
The research team also found that the mechanism was dependent on brown adipose tissue, which is 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 the active endocrine organ because it secretes molecules that communicate with other tissues and manage metabolism. It also helps in releasing stored energy and may promote weight reduction and metabolic health.
“There is ample evidence that obesity and the metabolic syndrome are linked to chronic inflammation that leads to systemic insulin resistance, so stopping inflammation in obesity may offer promising treatments for obesity-related diseases,” said co-author Dr. Yu-Hua Tseng. ., Senior Researcher in the Integrative Physiology and Metabolism Section of the Joslin Diabetes Center and Professor of Medicine at Harvard Medical School.
“We found that exposure to cold reduced inflammation and improved obesity metabolism, at least in part through activation of brown adipose tissue. These findings suggest a previously unrecognized function of brown adipose tissue in promoting inflammation relief in obesity. ‘
In two previous experiments, Tseng and colleagues found that brown fat can be activated by exposure to cold to produce certain lipid mediators that control nutrient metabolism. In the current study, scientists identified a new role for the lipid mediator produced from brown fat in the treatment of inflammation.
In the current study, scientists created a mouse model that develops obesity following the standard high-fat Western diet.
When animals have been exposed to a cold environment (around 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.
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.