Researchers have found a way to manipulate the metabolism and possibly prevent obesity and diabetes.
Previous work has found that a 20 per cent drop in calorie intake may prevent metabolic diseases caused by a high-fat diet. A similar benefit may be gained from resveratrol, a naturally occurring constituent of red wine.
Now a team led by Professor Johan Auwerx of the Swiss Federal Institute of Technology in Lausanne, Switzerland, has investigated the pathways involved in an effort to replicate the benefit using a drug.
They focused on an enzyme called SIRT1, which they describe as a “metabolic sensor”. In the experiments, mice were fed a high-fat diet for 15 weeks, while receiving a newly-developed drug at a range of doses.
Animals on higher doses did not become obese. In addition to being protected against diet-induced obesity, these mice did not develop any of its negative metabolic consequences which raise the risk of diabetes, such as impaired glucose tolerance and insulin sensitivity.
Mice on higher drug doses were also able to run twice as far as untreated mice. The researchers conclude that drug activation of SIRT1 promotes fat consumption in skeletal muscle, liver, and brown adipose tissue.
This could help protect humans too, they believe. Details appear in today’s (November 5) issue of Cell Metabolism.
Dr Auwerx said: “These results show that new synthetic SIRT1 activators can reproduce the positive metabolic effects that were previously demonstrated using resveratrol.
“But unlike resveratrol, these new chemical entities target only the SIRT1 pathway, making them more selective and potent for achieving these metabolic benefits.”
Auwerx, J. et al. Cell Metabolism, Vol. 8, Issue 5, November 5, 2008.
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