Gaining ground on losing pounds: How a little more fat might help combat the obesity crisis

Author: Holly Wobma, 02/05/13

Brown adipose tissue (brown fat). Photo by Alessandra Pasut

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I am, admittedly, the least ambitious type of gym-goer. I don’t train for marathons. I don’t try to body-build – the bar is set pretty low (and, incidentally, also the resistance!).

All I want to accomplish is to get rid of some of my “extra skin” and replace it with muscle. Because let’s face it, between having your body’s frame blanketed in fat or muscle, most of us would choose the less floppy option.

Interestingly, the same dichotomous choice is made by our muscle stem cells (“satellite cells”), and convincing them to choose “fat” more often may prove to be beneficial in fighting obesity.

It’s delightfully unintuitive, but let me be clear, I am not talking about the type of fat that you find in a Big Mac. I’m talking about brown fat.

Unlike the white fat that we often refer to in our everyday lives, brown fat has a very different role. It is highly metabolic and has an “uncoupling mechanism” that causes energy to be dissipated as heat rather than stored. It’s a caloric furnace, if you will. This furnace is taken advantage of by babies as an extra mechanism for warmth, but brown fat is quite scarce in adult humans, and, oddly, is more prevalent in lean and healthy individuals.

In a fascinating paper just published in Cell Metabolism, Michael Rudnicki’s group at the Ottawa Hospital Research Institute uncovers the mechanisms by which brown fat is synthesized. They reveal that a gene called Pdrm16 is necessary to coerce satellite cells into becoming brown fat, and that this protein is generally knocked out by a specific microRNA called miR-133. So, when we experience muscle injury, miR-133 knocks out the Pdrm16 gene, which then tells our satellite cells to progress along the “muscle” path. The study also confirmed that extended exposure to cold causes a reduction in miR-133, which then allows more brown fat tissue to be created in order to generate warmth.

Importantly, Dr. Rudnicki’s group then demonstrates that by administering a miR-133 antagonist into mice, they can recover Pdrm16 expression and induce the formation of functional, metabolically active brown fat. The consequence? Their mice show better glucose tolerance, better whole body metabolic activity, and a greater resistance to diet-induced obesity.

It thus seems clear, as discussed in one of my recent posts, that microRNAs are becoming increasingly interesting therapeutic targets for a wide variety of health conditions. Since this is still a relatively young field of research, however, a number of additional studies will have to be conducted before this microRNA-based therapy can be used clinically. For example, given that each microRNA has the potential to affect hundreds of different targets, I’d be curious to know whether miR-133 can influence gene targets beyond cell metabolism and thereby lead to other clinical effects. I’m also curious as to the type of strategy that would be used to introduce the miR-133 antagonists into a person and how long a single intervention would improve a person’s metabolic activity. Such details are difficult to predict based on experimental mouse models.

Regardless of the pharmaceutical strategy that may ultimately be used, Dr. Rudnicki has provided us with critical insight into a fundamental mechanism for weight control. In a world where obesity rates have reached epidemic proportions, the “weight” of this discovery should be quite evident.

Citation:
Yin H et al. (2013). MicroRNA-133 Controls Brown Adipose Determination in Skeletal Muscle Satellite Cells by Targeting Prdm16, Cell Metabolism, 17 (2) 210-224. DOI:

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Holly Wobma

Holly Wobma

MD/PhD student at Columbia University
Holly is an MD-PhD student at Columbia University in New York. She recently (2011) completed a Bachelor of Health Sciences Honours Degree from the University of Calgary, where she pursued research related to nanotechnology and regenerative medicine. In addition to research, she enjoys participating in science outreach roles. Previously, she contributed to an award-winning Nanoscience animation produced by the Science Alberta Foundation (“Do You Know What Nano Means?”), and served on the board of directors for the Canadian Institute for Photonic Innovations Student Network.
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