Brown Fat Research Heats Up, Fuels Dreams of Weight Loss

By Jeffrey Norris

Brown fat combined with a stimulating environment helps burn off calories, at least if you’re a mouse, and maybe even if you’re a human.  

Shingo Kajimura, PhD

Shingo Kajimura, PhD

According to a study by Ohio State University researchers published in the Sept. 7 issue of the scientific journal Cell Metabolism, groups of mice maintained in spacious surrounding with frequently changed mazes and toys ended up with about 50 percent less belly fat after four weeks compared to groups of mice living in standard laboratory enclosures. The study authors believe the result is due to a hormone released from the brain’s hypothalamus that acts biochemically downstream on the fat cells.

The mice converted fat-storing white fat cells – the stuff most of us are trying to lose – to fat-burning brown fat cells, which generate heat. They also made new brown fat cells. As a result, they remained svelte, in a rodent-kind of way.  And although another group of mice that had only running wheels moved more than a mile more per day than the more stimulated mice, they lost less fat.

UCSF Diabetes Center brown fat researcher, Shingo Kajimura, PhD, says there is plenty of reason to be excited about brown fat research in humans as well as in mice.

“If you have more fat, you may have less brown fat," says Kajimura, who also is a member of the Department of Cell and Tissue Biology. "If you have more brown fat you tend to be lean.”

In other words, if you want to lose weight, brown fat might be your friend.

As far as human studies go, “Those are correlation studies – they do not establish a causal relation,” Kajimura says. “But a causal relationship has been established in genetically modified mice that make more brown fat and are leaner as a result.”

Brown fat was long appreciated to be a lifesaver for cold weather hibernators such as bears. Babies have some too, to help keep them warm despite their lack of shivering muscle bulk to generate heat.

But brown fat research suddenly began attracting intense interest just a few years ago when researchers discovered that adults retain their own small, distinct reservoirs of brown fat. There are roughly 50 grams of the stuff in these newly discovered depots. That amount of brown fat, when activated, is enough to burn off more than eight pounds per year, researchers have estimated.

Brown fat cells are brown because they have so many cellular power plants, called mitochondria, burning fuel within them, according to Kajimura.

Kajimura, who recently equipped a new lab in the stimulating environment of the Ray and Dagmar Dolby Regeneration Medicine building at UCSF, is well regarded in the brown fat research community. This is due in part to his earlier research, published in 2009 in Nature, in which he showed that a pair of proteins can be used to convert common fibroblast cells from the skin into calorie-burning brown fat in animals. In the Ohio State study the researchers found that one of the proteins identified earlier by Kajimura was switched on to “brown” some cells within the white fat mass, enabling them to burn more calories by generating heat.

By manipulating proteins such as these, Kajimura says, “We want to engineer fat cell quality to control energy expenditure.” Instead of constantly reminding you to exercise and eat right, he wants to find a drug that will turn your white fat to brown fat, a goal shared by some in the pharmaceutical industry. “We just started,” he says.

Earlier research showed that human brown fat cells are activated after exposure to cold for several days. ”This paper shows that environmental enrichment may be an alternative to chronic exposure to cold as a pathway to induce more heat generation through brown fat,” Kajimura says.

Let’s see – the road to weight loss may involve sitting out in the cold for a week, or alternatively, doing new and cool things with your friends. Tough decision.

But again, Kajimura cautions that the results so far are from just one study, and the research was on mice, not humans. While the benefits of triggering heat production when you’re in the cold are clear, “I am not quite sure what the real biological meaning is for these new findings,” he says. “Maybe brown fat does something else in addition to producing heat,” he speculates.

While cold exposure already has been shown in humans to rev up calorie burning by brown fat, this new link between a stimulating environment and fat loss due to brown fat conversion remains to be demonstrated. In addition, Kajimura suggests that the brain hormone cited by the study authors is not necessarily the trigger for the changes in fat composition observed in the study.

The Ohio State researchers found that in the absence of the hormone brain-derived neurotrophic factor (BDNF), the conversion of white fat to brown fat did not occur. The same scientists previously published research in which they found that mice in enriched environments make more new nerve cells and learn and remember better than mice in standard lab environments.

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