ABOVE: White (L), beige, and brown (R) fat cells Modified from © ISTOCK.COM, Viki

Applying heat locally activates beige fat in mice and humans, and could become an approach to tackle obesity, a study published today (March 4) in Cell suggests. 

“Overall, they suggest a fascinating and very easy to translate observation, by applying that mild heat you might activate thermogenic adipocytes. But in humans the situation is definitely more complicated,” Siegfried Ussar, an obesity researcher at Helmholtz Munich, Germany, who was not involved in the study, tells The Scientist. “It will be interesting to see how that translates to humans, because the nature of the cell types is still controversial plus the impact on the blood flow might be different.” 

See “Q&A: Brown Fat Linked to Better Cardio and Metabolic Health

Adipose tissue comes in three colors: white, brown and beige. While white fat specializes in storing lipid and expands during obesity, brown fat is thermogenic, turning energy into heat. Beige fat is the middleman: beige fat cells are located within white fat and are indistinguishable from them, unless they undergo a process called browning. After browning, beige fat burns energy and produces heat. “We want to understand how we can activate beige fat to prevent or treat obesity,” Xinran Ma, an endocrinologist at East China Normal University in Shanghai, China, who co-authored the new study, tells The Scientist. 

Previous research by other groups had sought to induce browning through various stimuli, including cold treatment and the activation of beta-adrenergic signaling. In the present study, the researchers used a different stimulus: heat, applied just to a region thought to harbor beige fat. The researchers used nanoparticles, which they injected into white fat found around the groin of mice. When exposed to near-infrared light, the nanoparticles heat up the tissue around them to about 41°C. And when the researchers induced this temperature for 10 minutes in mice, they observed increased heat production in the area after 12 hours using thermal imaging—an indication that at least some of the area’s beige fat had browned.

The researchers then tested local hyperthermia therapy in humans by applying a heat source of 41°C to fat deposits around the neck and the shoulders, where beige fat is thought to be found in humans. Again, internal heat production in the area increased, and remained elevated for two hours after the external heat source was removed, based on thermal imaging. From that, the authors concluded that local hyperthermia could induce thermogenesis in humans by activating beige adipocytes. 

Roland Stimson, an endocrinologist at the University of Edinburgh in the UK who was not involved in the study, questions in an email whether this heat production is attributable to brown adipose tissue (BAT) thermogenesis. “It would be important in future work by the authors to use another imaging modality such as PET/CT to determine whether BAT was activated specifically, as thermal imaging can be influenced by many factors such as blood flow, vasodilatation, [and] skeletal muscle heat production.”

The principal observation is interesting; how this, however, will translate to any benefit to humans is a little bit unclear.

—Siegfried Ussar, Helmholtz Munich

In the study, the researchers also looked at how metabolism changed after local hyperthermia therapy. In mice fed a high-fat diet and treated with local hyperthermia therapy, they observed reduced body weight, enhanced insulin sensitivity, smaller adipose deposits, and less fatty livers, compared to mice fed a high-fat diet but not exposed to local hyperthermia. 

The study authors had previously studied the role of the protein heat shock factor 1 (HSF1) as a regulator of energy expenditure, so they investigated whether HSF1 might play a role downstream of heat therapy in their rodent models. They found that mice engineered to lack HSF1 in fat cells had higher body weights and fat masses when fed a high fat diet, and couldn’t heat their bodies as well, suggesting a reduced capacity for fat browning. In humans, genome- and exome-wide association study datasets identified a single nucleotide polymorphism in the HSF1 gene that was associated with decreased body mass index (BMI) and serum triglyceride

Ussar says the study indicates a link between HSF1 and the browning of beige fat, as HSF1 knockout mice exhibited reduced browning across the board. He adds that “to what extent this is really the only mechanism by which mild heat exposure translates to the tissue beiging is not clearly established, and [it is] not a hundred percent certain to go via the HSF1 pathway.”

Ma suggests the findings could be translated to humans and help fight obesity. “If you just keep [the neck] warm [to some degree], it can also burn some energy. This is a lifestyle change, keeping this part warm is helpful for your health.” 

Stimson is cautious about extending the results that far. “It would also be important to measure whole body energy expenditure following the treatment to see if this did increase in line with enhanced thermogenesis, as this would be key to determine the therapeutic potential of this approach,” he says. 

Ussar has similar reservations. “The principal observation is interesting; how this, however, will translate to any benefit to humans is a little bit unclear,” he says. He also says he wonders why, if local heat therapy is so effective, the observed metabolic effect of this intervention has not been reported before. “There are millions of people every day wearing heat patches on their neck because they have muscle pain. And as far as I know, no one has ever reported any metabolic benefits from that.”