The Obesity Research Laboratory works on the consequences of the excess of fat mass observed in obesity and aims at understanding the biological determinants and molecular mechanisms of obesity-related metabolic complications with a special emphasis on type 2 diabetes.
We have studied novel aspects of fatty acid metabolism in adipose tissue and skeletal muscle as well as the links between metabolic, inflammatory and fibrotic pathways and their relationship with lipotoxicity and insulin resistance. Using a bedside-to-bench approach, we have shown that modulation of adipose tissue and skeletal muscle lipolysis impacts on fat oxidation, lipotoxicity and insulin sensitivity. Studies in mice and humans revealed that pharmacological (inhibition of lipolysis, treatment with natriuretic peptides) and lifestyle (physical exercise, low calorie diet) interventions improve adipose tissue and skeletal muscle function as well as whole-body insulin sensitivity. In fat cells, inhibition of lipolysis or activation of fatty acid oxidation shows beneficial effects by limiting fatty acid release into blood circulation and by intrinsic modulation of glucose metabolism. Moreover, recent studies revealed a physival interaction between one of the fat cell neutral lipase and a transcription factor governing insulin signaling independently of lipolysis. In skeletal muscle, the regulation of intramyocellular triglyceride metabolism by lipases and of fatty acid oxidation by natriuretic peptides may be protective against the deleterious role of excess circulating fatty acids in obesity.
Our overall objective is now to decipher the cellular and molecular mechanisms associating fatty acid and glucose metabolisms at tissue and whole body levels and to evaluate the therapeutic potential of the inhibition of adipose tissue lipolysis/lipases and activation of skeletal muscle and adipose tissue fatty acid oxidation.
