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Harvard Scientists Discover How Cold Temperatures Could Help You Lose Weight

Researchers have found that cold temperatures help fight obesity and related metabolic diseases by reducing inflammation.

Brown adipose tissue is activated by cold and releases anti-inflammatory compounds.

Over 40% of adult Americans are obese, a complex condition that increases the risk of diabetes, heart disease, and some types of cancer. By causing low-grade chronic inflammation and accumulation of immune cells in insulin-sensitive tissues, obesity is one factor that may contribute to other health problems. Scientists believe that reversing or “resolving” this chronic inflammation could delay the development of obesity-related diseases such as diabetes and possibly facilitate weight loss.

Researchers at Brigham and Women’s Hospital and the Joslyn Diabetes Center found that exposing diet-induced obese mice to cold improved insulin sensitivity and glucose tolerance and eliminated obesity-induced inflammation. Their findings were reported in a new paper published in. natural metabolism.

“We found that cold exposure reduces inflammation and improves metabolism in obesity, which is mediated, at least in part, by activation of brown adipose tissue.” — Dr. Yu-Hua Tseng

The researchers also found that this mechanism relies on brown adipose tissue, commonly referred to as “good fat,” to release a natural 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 manage metabolism. It may also help release stored energy, promoting weight loss and metabolic health.

“Because extensive evidence indicates that obesity and metabolic syndrome are associated with chronic inflammation leading to systemic insulin resistance, disrupting obesity inflammation is a promising treatment for obesity-related diseases. “It could be,” said co-author Yu-Hua Tseng, Ph.D., a senior researcher in the Integrative Physiology and Metabolism Section of the Joslin Diabetes Center and a professor of medicine at Harvard Medical School.

“We found that cold exposure reduces inflammation and improves metabolism in obesity, which is mediated at least in part by activation of brown adipose tissue. It suggests a previously unrecognized function of brown adipose tissue in promoting resolution of inflammation.”

In two previous experiments, Tseng and colleagues found that cold exposure could activate brown fat to produce specific lipid mediators that control nutrient metabolism. In this study, researchers identified a novel role for lipid mediators produced from brown fat in resolving inflammation.

In the current study, researchers created a mouse model that develops obesity when fed a standard high-fat Western diet.

When animals are exposed to cold environments (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.
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.



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