Drosophila as a model for studying obesity-induced inflammation and cardiac dysfunction

Studies to date have suggested that in obesity immune cells infiltrate the adipose tissue and promote a lowgrade chronic inflammation. This has been linked to altered adipocyte metabolic function and to perturbations in lipid metabolism, including enhanced lipolysis, a process active in fat cells during starvation and enhanced in the fat cells of obese people. Recent data showed that free fatty acids (FFA) produced during lipolysis in obese people function as chemoattractants for macrophages in adipocytes. But how are macrophages recruited to the adipose tissue? To answer this question, we are taking advantage of a previously unrecognized conserved functional relationship in Drosophila between the immune cells called hemocytes (macrophage like cells) and adipocytes (larval fat body, FB). Drosophila FB- a metabolic tissue with similar physiological functions to the mammalian adipose tissue and liver - acts as a functional unit to control key metabolic processes and the native immune response in addition to storing fats and sugars. By reducing the level of ecdysone, the hormone responsible for controling development and growth, we obtain larvae that continue to grow until reaching an "obese-like" phenotype. These animals have a high content of triglycerides and FFA, increased levels of glucose from trehalose in the hemolymph and insulin resistance. Our data also show that obese larvae have a high number of hemocytes in the FB, which is increased during lipolysis. In addition, we observed increased cardiac contractility in obese animals, a condition that resembles heart dysfunction described for obese people. Our data demonstrate for the first time that immune cell infiltration into adipose tissue is an evolutionarily conserved process and provide an opportunity to develop a model in Drosophila to study the programs that are critical for immune cell recruitment to adipose tissue.