New genetic switch clue to sustainable weight loss

2 March 2016

New research into obesity may have identified a molecular mechanism that influences so-called ‘yo-yo dieting’.

Losing weight can be a battle and maintaining that new found healthy weight can be even more of a challenge, leading to an unhealthy cycle of extreme dieting, weight gain, extreme dieting and so on. 

Scientists have identified the enzyme histone deacetylase 5 (HDAC5) as playing an important role in triggering leptin signalling. Leptin, sometimes called the ‘satiety hormone’, helps to regulate food intake by letting the body know when it has taken in the amount of energy it needs, that is, it helps to control hunger. Severe leptin deficiency is associated with one of the few types of ‘monogenic obesityi.e. obesity where a single gene has been causally linked. 

Working with mice, the research team based at the Helmholtz Diabetes Center in Germany found that inhibiting HDAC5 activity in the hypothalamus, the area of the brain where energy levels are controlled, resulted in significant impairment in leptin sensitivity. Not realising their energy levels were back in balance, the mice kept eating beyond their bodies' needs and they gained weight. Conversely, with targeted stimulation of hypothalamic HDAC5  leptin action was improved, partially protecting against obesity.

Study author Dr Paul Pfluger commented that while diet and exercise continue to be essential factors in sustainable weight loss, “individual components of the leptin effect (such as HDAC5) could be potential drug targets”, although he concluded, "It remains to be seen in the coming years whether this enzyme will be a suitable target for combating obesity in humans."

The research was published in Nature Communica tions earlier this week.

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