Fighting Fat with Fat

Many Americans shell out millions each year in search of the right diet or exercise program - all in an effort to shed some fat. But there's one type of fat that most would actually want to hold on to: brown fat. Researchers in Japan and throughout the world have been looking for ways to restrain the power of brown fat cells to burn fat more efficiently for decades, a kind of tissue that acts as a natural furnace. The jackpot would be to develop a drug that could make our bodies produce more brown fat, or to crank up the activity of the brown fat we already have.

Dr. Shingo Kajimura recognized fat as something much more theoretical and acceptable. At his lab at the University of California, San Francisco, he studied how to build fat cells to combat obesity. Experts have long known that there are 2 types of fat - energy-storing white fat and energy- burning brown fat. Brown fat works in the opposite manner of white fat. White fat is known for storing extra calories as overflowing bellies, muffin tops, love handles and plump thighs. It is the fat that people try to eliminate with New Year’s diets and exercise regimens. In contrast, brown fat expends energy in the form of heat. This is very handy for maintaining body temperature in newborns, but brown fat takes up so little space that until recently most doctors believed adults had none. Likewise, the hibernating mammals such as bears, store large quantities of brown fat, which allows them to withstand winters.

Researchers have found that adults don't, in fact, lose all of their brown fat to the creeping ubiquitousness of white fat. With that finding, they've launched a scramble to discover how the substance's fat-burning abilities could be harnessed for weight loss. Other papers, published in the same issue of the New England Journal of Medicine and elsewhere since then, have confirmed and extended these original observations. “It just doesn’t happen every day,” says Dr. Gregory Steinberg, the Canada Research Chair in metabolism and obesity, and professor at McMaster University’s department of medicine. Joslin’s C. Ronald Kahn, M.D., Aaron Cypess, M.D., Ph.D., and their colleagues looked for brown fat in the radiology scans of adults who had undergone testing for other reasons. They found small collections of brown fat in the neck and around the collarbones that tended to show up in younger, leaner adults examined in cooler seasons, while these collections were not seen in older, obese individuals. Women had detectable brown fat twice as often as men.

Unlike white fat cells, brown fat cells contain a lot of mitochondria, which are the cells’ power plants. These mitochondria are rich in iron, which give the cells their brown colour.

Despite the fact that he wasn’t involved in the 2009 research, Steinberg demonstrates the analysis of brown fat in adult humans lead through a new outlet to align energy imbalances that lead to obesity. While diets and appetite-suppressing drugs can effectively reduce energy intake, they often make people feel cranky and miserable. And increasing energy expenditure can be tricky too. If you’ve ever tried losing weight through exercise alone, you’ll understand how difficult it is to work off that morning doughnut or post lunch cheesecake at the gym. Plus, the hardest part for most people isn’t losing extra weight; it’s trying to keep that weight off.

The entity of brown fat means it now may be possible to control energy imbalances by taking advantage of this natural furnace, Steinberg says. Other than exercise, “if you want to affect energy expenditure, this is really the only way to do it.” The question is how? Within the past few years, scientists have experimented with multiple possibilities, from tinkering with certain enzymes, hormones and stem cells, to learning how brown fat communicates with the brain through the nervous system. While this work is primarily being conducted on lab animals, there’s promise it could lead to the development an effective therapy for humans in the not-too-distant future.

Transforming white fat into brown

Obesity happens when energy intake exceeds energy expenditure. Brown fat may help balance the equation, if scientists can harness the energy-burning power for clinical application. Brown fat is not a cure for obesity, but burning off a hundred or more extra calories a day could add up. “This is very encouraging to us, because that means if you don’t have it ... then probably we can promote this browning of white fat,” express by Kajimura. “Brown fat seems not only to disappear with obesity but also with age, he says, which may explain age-related obesity. When people reach their 50s and 60s, around the same time they seem to lose brown fat, they commonly gain weight, even though their appetites don’t typically change, he added. He goes on to say that the reason brown fat seems to vanish in older adults is unknown.

Additionally, studies in mice show that brown fat activity appears to reduce the metabolic complications of obesity, such as high blood sugar levels and low insulin sensitivity, even if the mice don’t lose weight. The catch is, Kajimura explains, if you stop treating the mice, it appears this brown fat turns back into white. For pharmaceutical companies, this is good news, as it means they could potentially keep selling the treatment, he says. But it does raise the question of how we may be able to keep brown fat longer.

Turning stem cells into brown fat

Ottawa scientists have found a trigger that turns muscle stem cells into brown fat, a form of good fat that could play a critical role in the fight against obesity. The findings from Dr. Michael Rudnicki's lab, based at the Ottawa Hospital Research Institute, were published in the prestigious journal Cell Metabolism. When he and his research team removed a short nucleic acid sequence called microRNA-133, the muscle stem cells of mice efficiently turn into brown fat His finding shows this same effect occurs by simply exposing mice to cold. “They shiver, and the muscle stem cells turn into brown fat,” he says. “Of course, all of us would be quite thin if it weren’t for central heating,” he adds.

The fact we can maximize the calorie-burning power of brown fat simply by being chilly certainly sounds alluring. Unfortunately, ramping up our brown fat through cold exposure isn’t ideal. “People don’t really want to sit around in their underwear in their house at 5 or 10 degrees Celsius, because it’s uncomfortable,” Steinberg says, adding that cold exposure also prompts people to eat more, which would likely offset any benefits.

Inhibiting serotonin

Steinberg is trying to consider another way to generate brown fat activity. He proposes the hormone serotonin, which exists at higher levels in the bodies of people with diabetes or who are obese, is a key target. He and his teams have discovered that constraining the body’s production of serotonin in mice switches on their brown fat, protecting them from developing obesity, fatty liver disease, and diabetes. The consequence, he says, is like turning up the thermostat in your house and opening the windows to keep your furnace running. “All this energy they were consuming was just going out the window through the brown fat.” Steinberg explains we actually have two pools of serotonin. “Periphery” serotonin, which circulates in the blood, never mixes with the serotonin in the brain. Obstructing periphery serotonin, Steinberg says, has a lot of therapeutic possibility and does not involve introducing artificial hormones. Rather, he says, “What we’re trying to do is bring back the levels of this hormone to what they normally are in a lean person.”

As encouraging as the promising analysis on brown fat may be, any therapies that arrive won’t likely eliminate the need for healthful eating and exercise. However, it can possibly blend with the current methods of weight control. “Diet and exercise works,” Kajimura says, noting the goal remains to reduce energy consumption and activate energy expenditure. “You have to combine the two.”