Research interest in free fatty acid-binding receptors has been growing during the last decade, with an aim to better understand the modulation of host physiology in response to nutrition. G-protein-coupled receptor 43 (GPR43), also called free fatty acid receptor 2 (FFA2/FFAR2), binds short-chain fatty acids produced by the microbial fermentation of carbohydrates and has shown promising therapeutic potential. Based on our current knowledge, GPR43/FFAR2 can be proposed as a key player in gut microbes-host crosstalk, although further research is needed to clearly evaluate its role in the management of host health by nutrients or treatments targeting the gut microbiota. I will present data evidencing that activation of GPR43/FFAR2 on leukemic cells reduces cell proliferation. Altogether, our data suggest that this mechanism can be exploited through the production of short-chain fatty acids by the gut microbiota upon fermentation of non digestible carbohydrates. The second part of my talk will focus on the in vivo and in vitro regulation of the GPR43/FFAR2 mRNA expression in the context of obesity and cancer. Finally, the role of GPR43/FFAR2 in human adipogenesis will be evoked.