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Loosing Weight by Being Cool: Brown Fat

I’ve always thought I knew exactly where the fat is on my body.  All I have to do is pinch myself at the waist to prove to myself that I wear it around me like a belt.  Pounds of it.

That’s what I thought until four months ago.  In April I learned that I have a whole additional reservoir of fat that I knew nothing about.  This revelation, a bit of a shock for someone who writes textbooks on this sort of thing, is of real importance, as it suggests a new way to approach the treatment of obesity.  It might even help me loose some of that fat around my waist.

Here’s the thing. The fat around my waist is what biologists call white fat. White fat stores calories as large liquid droplets of pure fat within individual cells. When my body gleans more energy from the food I am eating than it needs to run its daily operations, it stores the excess there, a metabolic savings account in the currency of liquid fat.

This other fat I have, the kind I didn’t know I carried, is located primarily behind the muscles of my lower neck and collarbone, and running along my spine.  Called brown fat, it does not store calories, but rather burns fat to generate heat. Imagine a metabolic bank clerk shoveling the body’s store of liquid fat currency into a fireplace. 

Brown fat cells are brown because they are crammed full of iron-rich mitochondria, the tiny sausage-shaped organelles within cells that convert glucose and fat into ATP molecules, the cell’s energy currency. Brown fat cells don’t make any ATP, however --  a special protein within the brown fat cells called UCP1 short-circuits this process, so that the calories simply burn away as heat.

Like small mammals, newborn human babies have lots of brown fat around their shoulder blades, burning liquid fat to keep warm.  Not for long, though. As the babe grows into an infant, it looses this heat-generating tissue, until as an adult it lacks any brown fat.  Or so we thought.

Not so, it turns out. In 2007 an experiment by a Swedish cancer biologist named Jan Nedergaard led to an odd observation. Nedergaard was using a very sophisticated form of body scan called positron emission tomography to trace tumor metastasis (that is, to track where tumor cells were moving in the body of a cancer patient). To do this, he administered as a tracer a fluorescent form of glucose, expecting to see increased glucose uptake in areas where the tumor had spread.  Instead he found in all of his patients, even ones without cancer, symmetrical areas of increased tracer uptake in the upper parts of the human body.  Perhaps, he surmised, this is brown fat tissue busily burning the glucose tracer.

Three independent studies published last April confirmed Nedergaard’s observation, and by biopsy proved definitively that the tissues he had identified were indeed brown fat.  In one of these studies, a typical individual carried 63 grams of brown fat, enough to burn in a year the amount of energy stored in about 4 kilograms (almost nine pounds) of white fat tissue.

As you might expect from its function in human babies, the brown fat tissue detected in these three studies burned fat far more ferociously when the body was cold. In all individuals, exposure to cold led to a 15-fold increase in metabolic heat generation (measured as glucose tracer uptake).  It is as if low temperature turns the furnace “ON.”

It should come as no surprise that obesity researchers have jumped on this discovery. Last week in the prominent journal NATURE researchers led by Bruce Speigelman of Harvard Medical School reported that the body uses a relatively simple system to convert tissue into brown fat cells. Their experimental approach was clever. Speigelman had learned from long study of white fat metabolism that a key step in making fat cells was the switching on of particular genes. This could only be done, he had found, by a special kind of regulatory protein shaped like a fist giving someone “the finger.”  This so-called zinc finger reaches into the spiral of a DNA molecule to switch on the genes.  To find out how humans make brown fat, Speigelman  simply disabled the zinc finger proteins in brown fat cells and then looked to see what kind of cells they reverted back to. 

They became muscle cells.  This is very surprising.  It has always been assumed that brown fat derived from white fat cells, but not so.  Brown fat is made from muscle cells. 

Speigelman has been able to go even further.  Using the appropriate zinc finger protein and one other regulatory protein, he has been able to convert mouse skin cells to brown fat cells!  Transplanted back into normal mice, these converted skin cells seem to work just fine as brown fat tissue.

Speigelman is currently carrying out the key experiment towards which all of this research is pointed, transplanting these brown fat cells into obese mice.  If the brown fat cells continue to do their thing, as earlier studies indicate they will, then the mice should loose weight – a lot of weight. 

Suggesting a novel if unconventional therapy for obesity, such a result would be exciting indeed.  Inserting 50-100 grams of brown fat cells into a person would enable him or her to burn off more than ten pounds of white fat a year.  I don’t know about you, but I sure could stand to loose ten pounds.

Of course, brown fat’s furnaces don’t turn on unless your body is cold.  This raises the fascinating possibility of weight loss programs involving sticking your feet into a bucket of cold water at different times of the day.  The possible titles of weight-loss best seller books are mind-boggling.

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