White fat may have several paths to a healthier brown
Babies get their adorable chubbiness from brown fat, which keeps them warm, but until 2009, scientists thought we lost this helpful type of tissue as we grew up. Since its discovery in adults, brown fat has been studied as a potential treatment for obesity and related health issues. Now a team at Boston University has sequenced the genes of different fat types, and found that white fat cells may be turned brown through several different mechanisms, including by way of an experimental chemotherapy drug.
White fat is the more common type of adipose tissue, with our bodies using it to store excess energy. But brown fat contains much more mitochondria, iron-rich organelles that burn glucose and lipids rapidly to generate body heat and create energy, fighting obesity and its run-on health effects in the process. Previous studies have explored how the growth of healthy brown fat can be increased, or how existing white fat can be converted, through high fish oil diets or blocking certain proteins in the body.
This process of conversion is called "beigeing," and the brown fat cells it produces were discovered as a third, genetically-distinct type of fat called "beige fat" a few years ago. Wanting to replicate that process, the Boston University scientists looked to a diabetes drug called Avandia, which on one hand has been shown to improve the function of white fat, but on the other, can cause weight and heart problems in some people.
"The ideal thing would be to have a drug that does all the good things Avandia does, without the side effects," says Stephen Farmer, senior author of the study. "A lot of research now is focusing on what exactly the 'beigeing' fat is, how it functions, and how we can activate it."
To study the process, the team experimented with two groups of mice: one healthy, and the other brought up on a high-fat, high-calorie diet. Then, these mice were divided again into a control group, plus three other groups that received different drugs: Avandia, an experimental chemotherapy drug named Roscovitine, and another called CL-316,243, which mimics how the body responds to external cold, a factor that's previously been linked to improved brown fat growth.
Eight weeks later, of these three promising leads, only the mice given Roscovitine showed any improvements, including lower blood glucose levels, reduced weight gain and increased levels of beige fat, without any ill effects.
Looking for other potential avenues of treatment, the researchers went on to analyze the genes of the different types of fat. By using transgenic mice whose fat cells glowed different colors – red for white fat, and green for brown – the team was able to separate and study the cells. They found that the brown fat cells could be divided into three genetically distinct types, according to how they were produced. Naturally-occurring brown cells had one genetic pattern, while those created through cold had another, and those induced by either Avandia or Roscovitine were different again.
The team calls these types of brown fat cells classic brown, beige and brite, respectively. Why they have different genetic patterns is still unknown, and they appear to include genes not normally associated with fat. But although only one of the drugs had positive effects, the research does suggest that multiple methods, including drugs, could be used to induce brown fat.
"This is a provocative study, which really illustrates that brown and beige fat are druggable targets in a meaningful physiological way," says Bruce Spiegelman, professor of cancer biology at Harvard Medical School. "Whether or not Roscovitine should be used is still an open question – it's a toxic drug – but this study shows that drugs can be used."
The research was published in the journal Cell Metabolism.
Source: Boston University
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