Dynamic changes in lipid droplet-associated proteins in the "browning" of white adipose tissues

Biochim Biophys Acta. 2013 May;1831(5):924-33. doi: 10.1016/j.bbalip.2013.01.015. Epub 2013 Jan 30.

Abstract

The morphological and functional differences between lipid droplets (LDs) in brown (BAT) and white (WAT) adipose tissues will largely be determined by their associated proteins. Analysing mRNA expression in mice fat depots we have found that most LD protein genes are expressed at higher levels in BAT, with the greatest differences observed for Cidea and Plin5. Prolonged cold exposure, which induces the appearance of brown-like adipocytes in mice WAT depots, was accompanied with the potentiation of the lipolytic machinery, with changes in ATGL, CGI-58 and G0S2 gene expression. However the major change detected in WAT was the enhancement of Cidea mRNA. Together with the increase in Cidec, it indicates that LD enlargement through LD-LD transference of fat is an important process during WAT browning. To study the dynamics of this phenotypic change, we have applied 4D confocal microscopy in differentiated 3T3-L1 cells under sustained β-adrenergic stimulation. Under these conditions the cells experienced a LD remodelling cycle, with progressive reduction on the LD size by lipolysis, followed by the formation of new LDs, which were subjected to an enlargement process, likely to be CIDE-triggered, until the cell returned to the basal state. This transformation would be triggered by the activation of a thermogenic futile cycle of lipolysis/lipogenesis and could facilitate the molecular mechanism for the unilocular to multilocular transformation during WAT browning. This article is part of a Special Issue entitled Brown and White Fat: From Signaling to Disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Acylglycerol-3-Phosphate O-Acyltransferase / genetics
  • 1-Acylglycerol-3-Phosphate O-Acyltransferase / metabolism*
  • 1-Methyl-3-isobutylxanthine / pharmacology
  • 3T3-L1 Cells
  • Adaptation, Physiological
  • Adipose Tissue, Brown / cytology
  • Adipose Tissue, Brown / drug effects
  • Adipose Tissue, Brown / metabolism*
  • Adipose Tissue, White / cytology
  • Adipose Tissue, White / drug effects
  • Adipose Tissue, White / metabolism*
  • Adrenergic beta-Agonists / pharmacology
  • Animals
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cell Differentiation / drug effects
  • Female
  • Image Processing, Computer-Assisted
  • Immunoenzyme Techniques
  • Isoproterenol / pharmacology
  • Lipase / genetics
  • Lipase / metabolism*
  • Lipids / chemistry*
  • Lipolysis
  • Mice
  • Microscopy, Confocal
  • Phosphodiesterase Inhibitors / pharmacology
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction
  • Temperature

Substances

  • Adrenergic beta-Agonists
  • Cell Cycle Proteins
  • G0S2 protein, mouse
  • Lipids
  • Phosphodiesterase Inhibitors
  • RNA, Messenger
  • 1-Acylglycerol-3-Phosphate O-Acyltransferase
  • Abhd5 protein, mouse
  • Lipase
  • PNPLA2 protein, mouse
  • Isoproterenol
  • 1-Methyl-3-isobutylxanthine