Competing tissue-specific functions for the Tribbles-1 plasma lipid associated locus

PURPOSE OF REVIEW The pseudokinase Tribbles-1 (TRIB1) remains the focus of intense research since genome-wide association studies (GWAS) associated it with multiple cardiometabolic traits in humans, including plasma lipids and atherosclerosis. This review highlights recent advances in understanding the function of TRIB1 and what outstanding questions remain. RECENT FINDINGS Studies performed in a myeloid-specific Trib1 mouse model show that Trib1 contributes to foam cell formation, underscoring the importance of continued research into tissue-specific functions of TRIB1. Investigations of TRIB1 function in a 3D hepatic organoid model demonstrate that hepatic TRIB1 functions elucidated in mouse models are recapitulated in these organoid systems. Lastly, a recent study showed berberine, an existing lipid-lowering drug, to be acting via a TRIB1-dependent mechanism, highlighting both a novel regulator of TRIB1 expression and the potential of studying TRIB1 through existing therapeutics. SUMMARY TRIB1 remains one of the more fascinating loci to arise from cardiometabolic GWAS, given the constellation of traits it associates with. As genetic studies continue to link TRIB1 to metabolic phenotypes, more functional research on tissue-specific TRIB1, regulation of TRIB1 and its function in current therapies, as well as the reproduction of results from mice in human contexts are all necessary to increase our understanding of TRIB1 and its relevance.