Altered Lipogenesis in Liver and Brain in the context of Obesity:
Adipogenesis is the phenomenon where there is rampant metabolism that consequently accelerates metabolite-mediated epigenetic reprogramming. Mature adipocytes (fat cells) store excess energy by forming inert lipid droplets through several metabolic pathways, including Fatty acid synthesis. During this process, intermediate metabolites such as SCFAs (acetate, butyrate, crotonate, etc.) can be utilized by epigenetic enzymes to modify histones. A recent study from our lab has shown that p300-mediated histone lysine butyrylation increases during adipogenesis. By probing them with a small molecule, LTK-14A, we were able to inhibit p300-mediated butyrylation and consequently perturb adipogenesis without affecting the canonical acetylation reaction. Upon testing this molecule in different murine models, we have shown that LTK-14A can significantly curb obesity, liver steatosis and potentially liver fibrosis. We are also exploring the SCFA-mediated crosstalk between the Liver and Brain in the context of rare histone acylation modifications.
