Two Faces of Fat

Two Faces of Fat - NEWS FEATURE NATURE|Vol 447|31 May 2007...

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nwanted, unloved, yet often over- abundant, few have much regard for fat. Scientists, too, long thought of fat cells as good-for-nothing layabouts unworthy of attention; containers stuffed with energy to be released at the body’s command. So stuffed, in fact, that many other parts of the cell were thought too squeezed to function. So when, in the early 1990s, graduate stu- dent Gökhan Hotamisligil at Harvard Medi- cal School in Boston caught fat tissue doing something biologically remarkable, at first he did not believe his own data. He repeated the work many times, but it always came out the same: fat from obese mice was produc- ing TNFα — the hot inflammatory molecule of the day because of its role in autoimmune disorders such as arthritis. After he and his colleagues published their observation in Sci- ence 1 , others in the field remaned sceptical. Hotamisligil says he was invited to speak at meetings “for entertainment purposes”. Since then, fat cells have had an image change. This started with the 1995 discovery that fat secretes leptin, a hormone that tells the brain “I’m full, stop eating”. In retrospect, it makes sense that fat should tell the body how much energy it is storing and how much more to take in. But when it came to obesity-related problems such as type 2 diabetes and cardio- vascular disease, fat was still not seen as an active player. These conditions were thought to be caused by an excess of nutrients from overeating, or a glut of fatty molecules spilling out of storage into the bloodstream. More than a decade on, fat has a higher sta- tus. Scientists know that fat cells pump out ten or more molecules called adipokines that carry messages to the rest of the body. And ‘fat’ fat cells — those common in the obese and which are themselves bloated with lipids — send differ- ent molecular messages from ‘thin’ fat cells. The signals from ‘fat’ fat are thought to directly promote insulin resistance and to trigger inflammation, which may, in turn, cause type 2 diabetes, cardiovascular dis- ease, increased cancer risk and other obesity- associated problems. This means that it might be possible to treat these conditions without shedding the fat itself. Some remedies might be as simple as using anti-inflammatory drugs that have been around for more than a century; others might involve persuading obese fat cells to behave like skinny ones. Society may still view fat with resignation or even revulsion, but biologists have moved on. “No one appreciated the higher functions of fat,” says Barbara Kahn, a diabetes and obesity researcher at Harvard’s Beth Israel Deaconess Medical Center in Boston. “The fat THE TWO FACES OF FAT No longer viewed as inert packets of energy, fat cells are two-faced masterminds of metabolism. Kendall Powell
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Two Faces of Fat - NEWS FEATURE NATURE|Vol 447|31 May 2007...

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