Adipose tissue lipolysis controls monocyte homeostasis ; Importance de la lipolyse adipocytaire dans le contrôle de l’homéostasie des monocytes

Monocytes are key players in innate immunity mechanisms. They originate from the bone marrow and contribute to the whole-body homeostasis maintenance by being mobilized to the blood circulation in case of injury or chronic inflammation for example. There, monocytes can either stay in the blood circulation, or be recruited to peripheral tissues where they can differentiate into macrophages. Since the 70’s the metabolic control of immune cell survival, function and fate, mostly in macrophages that are involved in numerous cardio-metabolic diseases, gained great interest from the scientific community. However, the monocyte-specific metabolic control is still ill-defined. Interestingly, in steady state, blood monocyte numbers oscillate throughout the day on a 24h basis. Moreover, we highlighted a correlation between circulating monocyte number oscillation pattern and fatty acid levels during the day. Therefore, during my Ph.D. I focused on deciphering the possible causality that unites those phenomena and more particularly on studying the impact of energetic metabolites such as fatty acids on the control of monocytes. In this purpose, we generated a genetic mouse model deficient for the lipolysis adipose tissue key enzyme, namely Atgl. Here, we show that the inhibition of adipose tissue lipolysis leads to stress and specific chronic inflammation in the brown adipose tissue, associated to a local monocyte recruitment in a CCR2-dependant manner. This brown adipose tissue monocyte recruitment was paralleled to a decrease in blood monocyte numbers. However, we failed to see alterations in the bone marrow compartment, responsible for hematopoiesis and blood cell production. Thus, we highlighted the major role of adipose tissue lipolysis and monocyte recruitment on brown adipose tissue homeostasis. ; Les monocytes font partie des acteurs majeurs de l’immunité innée. Ils sont générés dans la moelle osseuse et contribuent à garantir le maintien de l’homéostasie de l’organisme en cas de blessure ou d’inflammation chronique ...