The transcription factor cyclic AMP-responsive element-binding protein H regulates triglyceride metabolism

Nat Med. 2011 Jun 12;17(7):812-5. doi: 10.1038/nm.2347.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apolipoprotein A-V
  • Apolipoprotein C-II / metabolism
  • Apolipoproteins / metabolism
  • Apolipoproteins A / metabolism
  • Cholesterol, LDL / metabolism
  • Cyclic AMP Response Element-Binding Protein / deficiency
  • Cyclic AMP Response Element-Binding Protein / genetics
  • Cyclic AMP Response Element-Binding Protein / physiology*
  • Humans
  • Hypertriglyceridemia / etiology
  • Hypertriglyceridemia / genetics
  • Lipoprotein Lipase / metabolism
  • Mice
  • Mice, Transgenic
  • Triglycerides / metabolism*

Substances

  • Apoa5 protein, mouse
  • Apolipoprotein A-V
  • Apolipoprotein C-II
  • Apolipoproteins
  • Apolipoproteins A
  • Cholesterol, LDL
  • Creb3l3 protein, mouse
  • Cyclic AMP Response Element-Binding Protein
  • Triglycerides
  • apolipoprotein A-IV
  • Lipoprotein Lipase