The epigenetic regulation of obesity
Adipose tissue is an important metabolic sensory organ. Mature adipocytes secrete numerous factors implicated in the regulation of energy balance, insulin sensitivity and cardiovascular disease. In addition, disorders such as obesity and lipoatrophy share very similar metabolic phenotypes, underscoring the homeostatic role of adipose tissue for health maintenance. Recent evidence highlights the importance of epigenetic regulation in adipocyte differentiation and function. As a result, identifying the epigenetic alterations in adipose-related disorders should aid in the development of new therapies for metabolic diseases. With this in mind, scientists on the EU-funded 'Polycomb and Trithorax group proteins: Master regulators of adipose tissue function?' (ATACC) project set out to investigate Polycomb proteins that are part of the chromatin-based transcriptional regulatory system. Initially identified in Drosophila, Polycomb proteins modify chromatin, thereby activating or silencing entire gene sets. To study the role of Polycomb proteins in metabolic control, researchers generated transgenic mice with tissue-specific deletions of Ezh2, Mll or Eed, and studied energy homeostasis, glucose metabolism and lipid homeostasis. Mice lacking Eed in the liver showed an improved metabolic profile, including glucose tolerance, insulin sensitivity and energy expenditure. Interestingly, mice were protected from diet-induced obesity and metabolic syndrome. Researchers also observed that Polycomb protein inhibition in the liver increased the secretion of hedgehog peptides, inducing brown adipose tissue formation. Taken together, ATACC results suggest that the Polycomb–hedgehog pathway cross-talk between liver and adipose tissue is vital for normal metabolic control. Most importantly, project work sheds light on the implication of chromatin remodelling in the development of human disease.
Keywords
Obesity, adipose tissue, metabolic disorders, Polycomb proteins, chromatin remodelling
