title: Tribbles-1: a novel regulator of hepatic lipid metabolism in humans.
abstract: The protein tribbles-1, encoded by the gene TRIB1, is increasingly recognized as a major regulator of multiple cellular and physiological processes in humans. Recent human genetic studies, as well as molecular biological approaches, have implicated this intriguing protein in the aetiology of multiple human diseases, including myeloid leukaemia, Crohn's disease, non-alcoholic fatty liver disease (NAFLD), dyslipidaemia and coronary artery disease (CAD). Genome-wide association studies (GWAS) have repeatedly identified variants at the genomic TRIB1 locus as being significantly associated with multiple plasma lipid traits and cardiovascular disease (CVD) in humans. The involvement of TRIB1 in hepatic lipid metabolism has been validated through viral-mediated hepatic overexpression of the gene in mice; increasing levels of TRIB1 decreased plasma lipids in a dose-dependent manner. Additional studies have implicated TRIB1 in the regulation of hepatic lipogenesis and NAFLD. The exact mechanisms of TRIB1 regulation of both plasma lipids and hepatic lipogenesis remain undetermined, although multiple signalling pathways and transcription factors have been implicated in tribbles-1 function. Recent reports have been aimed at developing TRIB1-based lipid therapeutics. In summary, tribbles-1 is an important modulator of human energy metabolism and metabolic syndromes and worthy of future studies aimed at investigating its potential as a therapeutic target.
authors.affiliation: Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA rcbauer@mail.med.upenn.edu.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Bauer
authors.affiliation: Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Batuhan O
authors.initials: BO
authors.lastname: Yenilmez
authors.affiliation: Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA Department of Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Rader
mesh_terms: D002318:Cardiovascular Diseases / Q000097:blood / Q000235:genetics / Q000378:metabolism; D055106:Genome-Wide Association Study; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D050356:Lipid Metabolism / Q000235:genetics / Q000502:physiology*; D008055:Lipids / Q000097:blood; D050155:Lipogenesis / Q000235:genetics / Q000502:physiology; D008099:Liver / Q000378:metabolism*; D008954:Models, Biological; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D008055:Lipids; C493170:TRIB1 protein, human; D017346:Protein Serine-Threonine Kinases
keywords: GWAS; Trib1; Tribbles; cardiovascular disease; lipid metabolism; lipoproteins