Mon, Sep-10-12, 02:24
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Plan: Muscle Centric
Stats: 238/153/160
BF:
Progress: 109%
Location: UK
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Muscles that do nothing can keep you warm and thin
Quote:
From The New Scientist
9 September, 2012
Muscles that do nothing can keep you warm and thin
Muscles that burn energy without contracting have yielded new clues about how the body retains a constant temperature – and they may provide new targets for combating obesity.
Traditionally, the body's main thermostat was thought to be brown fat. It raids the body's white fat stores in cold conditions to burn energy and keep the body warm.
Muscles also play a role in keeping the body warm by contracting and triggering the shiver response – but this is only a short-term fix because prolonged shivering damages muscles. Now it seems that muscles have another way to turn up the heat.
"Our findings demonstrate for the first time that muscle, which accounts for 40 per cent of body weight in humans, can generate heat independent of shivering," says Muthu Periasamy of Ohio State University in Columbus.
Surviving the chill
Through experiments on mice that had their usual thermostat – brown fat – surgically removed, Periasamy and his colleagues proved that a protein called sarcolipin helps muscle cells keep the body warm by burning energy, almost like an idling motor car, even if the muscles do not contract.
All of the mice had their brown fat removed, but some of them had been genetically engineered to lack sarcolipin too. These rodents could not survive when held at 4 °C, and died of hypothermia within 10 hours. By contrast, mice that could make sarcolipin were able to survive the chilly temperatures and maintained their core body temperature – despite having no brown fat.
Periasamy also showed that an inability to make sarcolipin made mice 33 per cent heavier than normal when fed a high-fat diet. This suggests that idling muscles might also help combat obesity by burning off excess energy. The search is now on for drugs that perform the same role, triggering idling muscles to burn off excess fat.
"The most interesting finding is that mice unable to make sarcolipin are more susceptible to obesity," says Andy Whittle of the University of Cambridge, who is testing spicy dietary treatments to ramp up the fat-burning activity of brown fat. "The research demonstrates that muscle is an important component even in mice, which have comparatively more brown fat than humans. In humans, burning fat in muscle is likely to be even more important for proper energy balance."
Journal reference: Nature Medicine, DOI: 10.1038/nm.2897
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http://www.newscientist.com/article...m-and-thin.html
Quote:
Sarcolipin is a newly identified regulator of muscle-based thermogenesis in mammals
The role of skeletal muscle in nonshivering thermogenesis (NST) is not well understood. Here we show that sarcolipin (Sln), a newly identified regulator of the sarco/endoplasmic reticulum Ca2+-ATPase (Serca) pump1, 2, 3, 4, 5, is necessary for muscle-based thermogenesis. When challenged to acute cold (4 °C), Sln−/− mice were not able to maintain their core body temperature (37 °C) and developed hypothermia. Surgical ablation of brown adipose tissue and functional knockdown of Ucp1 allowed us to highlight the role of muscle in NST. Overexpression of Sln in the Sln-null background fully restored muscle-based thermogenesis, suggesting that Sln is the basis for Serca-mediated heat production. We show that ryanodine receptor 1 (Ryr1)-mediated Ca2+ leak is an important mechanism for Serca-activated heat generation. Here we present data to suggest that Sln can continue to interact with Serca in the presence of Ca2+, which can promote uncoupling of the Serca pump and cause futile cycling. We further show that loss of Sln predisposes mice to diet-induced obesity, which suggests that Sln-mediated NST is recruited during metabolic overload. These data collectively suggest that SLN is an important mediator of muscle thermogenesis and whole-body energy metabolism.
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http://www.nature.com/nm/journal/va...ll/nm.2897.html |
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