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FAT VERSUS FAT
Brown fat can metabolize white fat through thermogenesis // It’s potentially the ideal weapon to fight obesity // And to provide therapy for metabolic diseases // Now the main question is how does it work?

The Fitter Fat

By David Howard // Photographs by Peter Hapak // Fall 2012
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Peter Hapak

Like many innovations in medicine, this discovery began as a problem. In the early 1990s, radiologists began using positron emission tomography, a type of body-scanning technology, to hunt for cancerous tumors. They would inject a dose of radioactive glucose into the bloodstream. Tumors consume glucose, so the PET scan would track the uptake of glucose in different parts of the body and might point the way to a previously unnoticed cancer.

Because glucose is a type of fuel, the radiologists knew that energy-burning organs such as the brain and the heart would suck up some of it. What they didn’t expect was that the glucose would also wind up being drawn to a region around the neck and shoulders, often in a symmetrical pattern. Tumors are generally not symmetrical in shape, so the radiologists were pretty sure what they were looking at was not cancer.

But what was it? In 2002, radiologists began routinely combining the PET technology with CT scans, which gave them a clearer view. They were stunned to realize that they were looking at brown adipose tissue, more commonly known as brown fat. For those specialists searching for malignancies, the brown fat was a nuisance, because its presence could obscure a tumor. But for researchers who study metabolism and obesity, the discovery of brown fat in adults was a watershed moment.

Brown fat is not actually fat, but rather a tissue that possesses a unique uncoupling protein, known as UCP1, embedded in its mitochondria. When the protein becomes activated under certain circumstances—for example, when a person is sitting in a cold room—it triggers a chemical reaction within the mitochondria that results in heat production. Like any fire, this process requires fuel, and brown fat maintains its heat partly by burning regular body fat, commonly known as white fat.

For decades, although researchers knew it existed in babies and animals, no one believed adult humans harbored brown fat, and its discovery in some adults—it’s still unclear how much of the human population possesses it—has opened the way for the medical research and pharmaceutical communities to pursue a compelling new kind of weight-loss treatment.

The stakes are potentially enormous. About one-third of all adults in the United States are obese and another third are overweight, according to the Centers for Disease Control and Prevention. The CDC forecasts that as many as one in three American adults could have diabetes by 2050, in some measure as a result of the projected rise in obesity rates. The direct annual medical cost associated with obesity exceeds $147 billion in the United States alone.

No one knows yet how significant a discovery of brown fat in humans might be. A sweeping new round of studies—some funded by drug companies—is aimed at finding ways to enhance the stores of brown fat in people who are overweight and to activate the tissue to do its work. Many researchers believe that in terms of the struggle to turn the dial back on obesity, brown fat might be the most important thing to come along for some time.

Brown fat has been the subject of fascination and controversy within the medical community for centuries. In 1551, Swiss naturalist Konrad Gessner characterized the tissue, which he observed in marmots, as “neither fat, nor flesh—but something in between.” Modern researchers began to grasp its potential significance in the 1960s, when a UCLA physiologist, measuring the vital signs of a marmot awakening from hibernation, noted that the animal’s temperature was higher than expected, and the scientist linked that fact to the marmot’s stores of brown adipose tissue.

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The Burning Question

Who will be the first to tap the potential of brown fat?

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hed-dossier

1.“Brown Adipose Tissue Oxidative Metabolism Contributes to Energy Expenditure During Acute Cold Exposure in Humans,” by Véronique Ouellet et al., The Journal of Clinical Investigation, Feb. 1, 2012. Previously, brown fat was thought to generate heat only in rodents exposed to cold; this small but groundbreaking study shows that in fact humans get the same warmth-giving, calorie-burning response from their cells in chilly climes.

2.“Beige Adipocytes Are a Distinct Type of Thermogenic Fat Cell in Mouse and Human,” by Jun Wu et al., Cell, July 20, 2012. This study establishes that the hormone irisin stimulates beige cells’ thermogenesis, raising hopes for a treatment for obesity and diabetes.

3. “Michael J. Stock: An Appreciation,” by Paul Trayhurn, International Journal of Obesity, September 2001. This paean to a pioneer in brown fat research is eye-opening for a number of reasons, not least the fighting within the field on the subject. Trayhurn notes that Stock’s inroads in the laboratory were “attacked with ferocity”—fascinating, given the enthusiasm for the topic among researchers today.

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