title: The transcription factor cyclic AMP-responsive element-binding protein H regulates triglyceride metabolism.
abstract: Here we report that the transcription factor cyclic AMP-responsive element-binding protein H (CREB-H, encoded by CREB3L3) is required for the maintenance of normal plasma triglyceride concentrations. CREB-H-deficient mice showed hypertriglyceridemia secondary to inefficient triglyceride clearance catalyzed by lipoprotein lipase (Lpl), partly due to defective expression of the Lpl coactivators Apoc2, Apoa4 and Apoa5 (encoding apolipoproteins C2, A4 and A5, respectively) and concurrent augmentation of the Lpl inhibitor Apoc3. We identified multiple nonsynonymous mutations in CREB3L3 that produced hypomorphic or nonfunctional CREB-H protein in humans with extreme hypertriglyceridemia, implying a crucial role for CREB-H in human triglyceride metabolism.
authors.affiliation: Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts, USA.
authors.forename: Jung Hoon
authors.initials: JH
authors.lastname: Lee
authors.forename: Petros
authors.initials: P
authors.lastname: Giannikopoulos
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Duncan
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Johansen
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Brown
authors.forename: Jorge
authors.initials: J
authors.lastname: Plutzky
authors.forename: Robert A
authors.initials: RA
authors.lastname: Hegele
authors.forename: Laurie H
authors.initials: LH
authors.lastname: Glimcher
authors.forename: Ann-Hwee
authors.initials: AH
authors.lastname: Lee
mesh_terms: D000818:Animals; D000072040:Apolipoprotein A-V; D053304:Apolipoprotein C-II / Q000378:metabolism; D001053:Apolipoproteins / Q000378:metabolism; D001054:Apolipoproteins A / Q000378:metabolism; D008078:Cholesterol, LDL / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D006801:Humans; D015228:Hypertriglyceridemia / Q000209:etiology / Q000235:genetics; D008071:Lipoprotein Lipase / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D014280:Triglycerides / Q000378:metabolism*
chemical_list: C499058:Apoa5 protein, mouse; D000072040:Apolipoprotein A-V; D053304:Apolipoprotein C-II; D001053:Apolipoproteins; D001054:Apolipoproteins A; D008078:Cholesterol, LDL; C500051:Creb3l3 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D014280:Triglycerides; C022205:apolipoprotein A-IV; D008071:Lipoprotein Lipase