The contribution of vitamin A to autocrine regulation of fat depots

Biochim Biophys Acta. 2012 Jan;1821(1):190-7. doi: 10.1016/j.bbalip.2011.06.004. Epub 2011 Jun 13.

Abstract

Morbidity and mortality associated with increased white fat accumulation in visceral fat depots have focused attention on the pathways regulating the development of this tissue during embryogenesis, in adulthood, and while under the influence of obesogenic diets. Adipocytes undergo clonal expansion, differentiation (adipogenesis) and maturation through a complex network of transcriptional factors, most of which are expressed at similar levels in visceral and subcutaneous fat. Rigorous research attempts to unfold the pathways regulating expression and activity of adipogenic transcription factors that act in a fat-depot-specific manner. Peroxisome proliferator-activated receptor-γ (PPARγ) is the master regulator of adipogenesis, and is expressed at higher levels in subcutaneous than in visceral depots. PPARγ expression in adipogenesis is mediated by CCAAT/enhancer binding proteins (C/EBPs) and several transcription factors acting in conjunction with C/EBPs, although alternative pathways through zinc-finger protein-423 (ZFP423) transcription factor are sufficient to induce PPARγ expression and adipogenesis. Vitamin A and its metabolites, retinaldehyde and retinoic acid, are transcriptionally-active molecules. Retinoic acid is generated from retinaldehyde in adipose tissue by the aldehyde dehydrogenase-1 family of enzymes (Aldh1). In this review, we discuss the role of Aldh1 enzymes in the generation of retinoic acid during adipogenesis, in the regulation of the transcriptional network of PPARγ in a fat-depot-specific manner, and the important contribution of this autocrine pathway in the development of visceral obesity. This article is part of a Special Issue entitled Retinoid and Lipid Metabolism.

Publication types

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

MeSH terms

  • Adipogenesis*
  • Adipose Tissue, White / enzymology
  • Adipose Tissue, White / metabolism*
  • Aldehyde Dehydrogenase 1
  • Animals
  • CCAAT-Enhancer-Binding Proteins / metabolism
  • DNA-Binding Proteins
  • Humans
  • Isoenzymes / metabolism
  • Mice
  • Mice, Knockout
  • Obesity / metabolism
  • PPAR gamma / biosynthesis
  • PPAR gamma / metabolism
  • Rats
  • Retinal Dehydrogenase / metabolism
  • Transcription Factors / metabolism
  • Tretinoin / metabolism*

Substances

  • Aldehyde Dehydrogenase 1
  • CCAAT-Enhancer-Binding Proteins
  • DNA-Binding Proteins
  • Ebfaz protein, mouse
  • Isoenzymes
  • PPAR gamma
  • Transcription Factors
  • Tretinoin
  • ALDH1A1 protein, human
  • Aldh1 protein, mouse
  • Aldh1a1 protein, rat
  • Retinal Dehydrogenase