Why do we get fat and why is it so difficult for so many people to keep off excess weight? DZD scientists at the Helmholtz Zentrum München, in collaboration with colleagues of Technische Universität München, have identified a new mechanism that regulates the effect of the satiety hormone leptin. The study identified the enzyme HDAC5 as key factor in our control of body weight and food intake and potential target against the Yoyo dieting effect.

The enzyme histone deacetylase 5 (HDAC5) has a significant influence on the effect of the hormone leptin. This hormone plays a crucial role in triggering satiety and thus on how the body adapts to a changing food environment. Mice unable to produce HDAC5 respond significantly worse to leptin – a condition referred to as leptin resistance. They show a continuously increased food intake and they get fat. Through targeted activation of HDAC5 the team was able to reverse this effect, and thereby enabling obese animals to loose fat mass and body weight.

The restoration of leptin sensitivity is an important step on the path towards sustainable weight loss and towards combating type 2 diabetes. However, it remains to be seen in the coming years whether HDAC5 will be a suitable target in humans.

Original publication:
Kabra, DG et al. Hypothalamic Leptin Action is Mediated by Histone Deacetylase 5. doi: 10.1038/NCOMMS10782. Nature Communications. February 29, 2016

Link to the publication:
http://www.nature.com/ncomms/2016/160229/ncomms10782/full/ncomms10782.html