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Rewriting Life

Obesity Fighter

A newly discovered hormone mimics the effects of exercise

Source: “A PGC1-α dependent myokine that drives brown-fat-like development of white fat and thermogenesis”
Bruce Spiegelman et al.
Nature
481: 463–468

Results: Researchers discovered a hormone that is produced when both mice and humans exercise. Increasing the levels of the hormone in mice resulted in some of the same benefits as exercise. It caused white fat, which stores energy, to turn into brown fat, which burns stored energy to generate heat. Mice that were given the hormone lost weight and showed a decrease in diet-induced insulin resistance, which is connected to diabetes.

Why it matters: The hormone may prove useful for treating diabetes and obesity. The discovery also sheds light on how exercise changes the way the body responds to sugar and utilizes fat.

This story is part of our March/April 2012 Issue
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Methods: Earlier research had shown that the protein PGC1-α is involved in regulating the expression of other proteins and is connected with exercise. The researchers identified five proteins controlled by PGC1-α. They discovered that one of these, FNDC5, is connected to the browning of fat cells and that FNDC5, in turn, is modified in cells and secreted as a hormone, which the researchers named irisin. They put mice and humans on a multiweek exercise regimen, after which they measured increased levels of irisin in both. They fed mice a diet high in fat to make them obese and insulin resistant. Then they introduced a gene into these mice that increased their production of the hormone. They measured the physical changes that resulted.

Next Steps: Ember Therapeutics, a company that the researchers founded before undertaking the study, is looking for ways to deliver the hormone therapeutically.

Muscle Enhancer

Changing proteins expressed in muscle allows mice to run farther

Source: “NCoR1 Is a Conserved Physiological Modulator of Muscle Mass Function and Oxidative Function”
Johan Auwerx et al.
Cell 147: 827–839

Results: By modifying proteins in muscle tissue, researchers increased muscle mass in mice and triggered other changes that improved the muscles’ ability to use oxygen. This allowed the mice to run longer: 80 minutes before they were exhausted, versus 60 minutes for control mice.

Why it matters: The finding could lead to treatments for muscular dystrophy and age-related muscle loss.

Methods: Researchers genetically engineered mice lacking in a protein, NCoR1, that works as something like a dimmer switch for other molecules in a cell, slowing the production of transcription factors that regulate the expression of genes. The protein seems to have different effects in different tissues. The researchers used a method that blocked the production of the protein only in muscle tissue and then measured changes in that tissue and in the animals’ behavior.

Next Steps: The researchers are searching for drugs that can selectively modulate the levels of NCoR1.

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