Americans spend over $60 billion a year to lose weight and yet two-thirds (that’s more than 200 million) are considered overweight or obese. Losing weight should be easy: just eat less and exercise more, right? But our body’s metabolism is a very complex thing and appears to fight against our best efforts to shed pounds. A recent analysis of clinical trial data and mathematical modeling suggests that over the long haul, none of the various diet strategies lead to meaningful weight loss. Even the contribution of exercise to weight loss has been called into question.
All is not lost. In fact, the fat we carry in our bodies may hold the key to overcoming our obesity woes. A recent CIRM-funded UC Francisco study published in Cell Metabolism finds that harnessing a calorie burning form of fat cells may help guard against the development of obesity.
The Many Hues of Fat
Humans, like other mammals, have two very different types of fat tissue. The more abundant white fat acts to store fat and provides a form of energy to help our body function. An excess of white fat tissue is associated with metabolic diseases including diabetes and obesity. Brown fat tissue, on the other hand, generates heat and is associated with slimness. It was thought that only babies have brown fat which protects them against cold temperatures – they lack the muscle strength for the shivering response – but research in 2009 identified this fat tissue in adults as well.
The UCSF team, led by professor Shingo Kajimura, showed last year that adults actually have so-called beige fat cells that are able to switch from white to brown fat in the presence of colder temperatures and vice versa. This discovery presents the tantalizing potential of promoting weight loss in people by pushing white fat cells toward energy burning brown fat. In that earlier work, the team identified a protein that when inhibited with drugs caused the white fat cells to burn energy like the beige and brown fat. But this effect was short lived and these cells reverted back to the typical features of white fat cells. Kajimura reflected on these previous studies in a university press release:
“Our focus has been on learning to convert white fat into beige fat. Now we’re realizing we also have to think about how to keep it there for longer time.”
In the new study, the team focused on the fact that as beige cells revert back to white cells, their mitochondria – a cell’s energy producing factories – begin to disappear. First author Svetlana Altshuler-Keylin wanted to understand why:
“We knew that the color of brown and beige fat comes from the amount of pigmented mitochondria they contain, so we wondered whether something was going on with the mitochondria when beige fat turns white.”
Stopping cells from eating up too much mitochondria
Examining gene activity as cells went from beige to white implicated a process called autophagy was at play. This house cleaning function of a cell involves the breakdown of its own internal structures that are not functioning properly or aren’t needed. So perhaps stopping the autophagy process from occurring would prevent the energy burning beige cells from eating up their own mitochondria and reverting them back to the energy hoarding white cells.
To test this idea, the team relied on mice lacking genes that play important roles in autophagy. They beefed up their beige fat by subjecting the mice to cold temperatures. But when returned to a normal environment, the mice kept their beige fat and it didn’t convert back to white cells. This change impacted the mice overall health: when place on a fatty diet for two months these mice with the defective autophagy gained less weight. These mice were also able to better regulate blood sugar levels, an indication they there were protected from type 2 diabetes symptoms.
While these results represent very early stage research, Kajimura and his team now have a solid path to travel toward trying to help obese individual burn more calories, especially as they age:
“With age you tend to naturally lose your beige fat, which we think is one of the main drivers of age-related obesity. Your calorie intake stays the same, but you’re not burning as much. Maybe by understanding this process we can help people keep more beige fat, and therefore stay healthier.”