A few recently published papers related to BET inhibition and/or BRD4 caught my eye on PubMed just now. The linkages between BET inhibitors and BRD proteins and various metabolic pathways keeps growing and growing!

BRD4 regulates adiponectin gene induction by recruiting the P-TEFb complex to the transcribed region of the gene.

Transcriptional regulation of autophagy and lysosomal function by bromodomain protein BRD4.

Muscle hypertrophy in hypoxia with inflammation is controlled by bromodomain and extra-terminal domain proteins.

I am particularly interested in the one regarding BRD4 regulation of adiponectin. Adiponectin, at least in mouse models, has been clearly shown to be necessary for adipocyte (fat cells) health. Adiponectin is secreted by the adipocytes and in turn binds to adiponectin receptors on adipocytes to help maintain adipocyte health and also binds to adiponectin receptors on peripheral tissues (such as liver, muscle, etc.). In general, these have effects to promote insulin sensitivity.

Of course, the study cited above are in mouse cells or transgenic mice in which BRD4 is depleted or knocked out, which is different than administering a pan-BET inhibitor or a bromodomain 2 selective BET inhibitor. But it definitely makes me wonder about the beneficial effects of apabetalone on adiponectin and adipose tissue.

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