Flipping a Genetic Switch on Obesity?

Illustration of a DNA switchWhen weight loss is the goal, the equation seems simple enough: consume fewer calories and burn more of them exercising. But for some people, losing and keeping off the weight is much more difficult for reasons that can include a genetic component. While there are rare genetic causes of extreme obesity, the strongest common genetic contributor discovered so far is a variant found in an intron of the FTO gene. Variations in this untranslated region of the gene have been tied to differences in body mass and a risk of obesity [1]. For the one in six people of European descent born with two copies of the risk variant, the consequence is carrying around an average of an extra 7 pounds [2].

Now, NIH-funded researchers reporting in The New England Journal of Medicine [3] have figured out how this gene influences body weight. The answer is not, as many had suspected, in regions of the brain that control appetite, but in the progenitor cells that produce white and beige fat. The researchers found that the risk variant is part of a larger genetic circuit that determines whether our bodies burn or store fat. This discovery may yield new approaches to intervene in obesity with treatments designed to change the way fat cells handle calories.

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Snapshots of Life: Fat (Tissue) Is Beautiful

Fat cells in 3D

Caption: Fat cells (red) surrounded by blood vessels (green) that supply them with nutrients.
Credit: Daniela Malide, National Heart, Lung, and Blood Institute; NIH

With all of today’s sophisticated microscopes, you’d think it would be simple to take high-magnification photos of fat—but it’s not. Fat tissue often leaks slippery contents, namely lipids, when it’s thinly sliced for viewing under a microscope. And even when a sample is prepared without leakage, there’s another hurdle: the viscous droplets of lipid contained in the fat cells block light from passing through.

So, it’s good news that one of NIH’s intramural scientists here in Bethesda, MD, has come up with a way to produce high-resolution, 3-D images of fat cells like the one you see above. Not only are these images aesthetically appealing, but they’ll be valuable to efforts to expand our understanding of this essential and much-maligned tissue.

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Fighting Obesity: New Hopes From Brown Fat

Artist rendition of a xray showing brown fat as glowing green

Caption: Brown fat—actually marked in green on this image—is wrapped around the neck and shoulders. This “shawl” of brown fat warms blood before it travels to the brain.
Illustration: John MacNeill, based on patient imaging software designed by Ilan Tal. Copyright 2011 Joslin Diabetes Center

If you want to lose weight, then you actually want more fat, not less. But you need the right kind: brown fat. This special type of fatty tissue burns calories, puts out heat like a furnace, and helps to keep you trim. White fat, on the other hand, stores extra calories and makes you, well, fat. Wouldn’t it be nice if we could instruct our bodies to make more brown fat, and less white fat? Well, NIH-funded researchers have just taken another step in that direction [1].

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Brown Fat, White Fat, Good Fat, Bad Fat

Photo of adipocytes in white adipose

Caption: Brown fat cells (stained brown with antibodies against the brown fat-specific protein Ucp1) nestled in amongst white fat cells.
Credit: Patrick Seale, University of Pennsylvania School of Medicine

Fat has been villainized; but all fat was not created equal. Our two main types of fat—brown and white—play different roles. Now, two teams of NIH-funded researchers have enriched our understanding of adipose tissue. The first team discovered the genetic switch that triggers the development of brown fat [1], and the second figured out how the body can recruit white fat and transform it into brown [2].

Why would we want to change white fat into brown? White fat stores energy as large fat droplets, while brown fat has much smaller droplets and is specialized to burn them, yielding heat. Brown fat cells are packed with energy generating powerhouses called mitochondria that contain iron—which gives them their brown color. Infants are born with rich stores of brown fat (about 5% of total body mass) on the upper spine and shoulders to keep them warm. It used to be thought that brown fat disappeared by adulthood—but it turns out we harbor small reserves in our shoulders and neck. Continue reading