Regulation of lipid droplet-associated proteins by peroxisome proliferator-activated receptors

• Published in: Biochimica et biophysica acta. Molecular and cell biology of lipids Vol. 1862; no. 10; pp. 1212 - 1220
• Main Authors: de la Rosa Rodriguez, Montserrat A., Kersten, Sander
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.10.2017
• Subjects: adipose tissue; Adipose Tissue - metabolism; Animals; droplets; enzymes; fatty acids; gene expression; Humans; Lipid droplet; Lipid droplet-associated proteins; Lipid Droplets - metabolism; liver; Liver - metabolism; macrophages; Macrophages - metabolism; Muscle, Skeletal - metabolism; organelles; Perilipins; peroxisome proliferator-activated receptors; Peroxisome Proliferator-Activated Receptors - genetics; Peroxisome Proliferator-Activated Receptors - metabolism; PPARs; skeletal muscle; transcription (genetics); triacylglycerols; Perilipins; Lipid droplet; Lipid droplet-associated proteins; PPARs
• ISSN: 1388-1981; 1879-2618; 1879-2618
• DOI: 10.1016/j.bbalip.2017.07.007

Excess fatty acids are stored in cells as triglycerides in specialized organelles called lipid droplets (LD). LD can be found in nearly all cell types and may expand during certain (patho)physiological conditions. The synthesis and breakdown of triglycerides and their deposition in LD is governed by a diverse set of enzymes and LD-associated proteins. These proteins serve structural roles in and around LD and regulate the activity of key lipogenic and lipolytic enzymes. The LD-associated proteins are subject to multiple regulatory mechanisms at the protein and gene expression level. A group of transcription factors that govern the expression of many LD-associated proteins are the Peroxisome Proliferator-Activated Receptors (PPARs). PPARs are lipid-activated transcription factors that play a key role in the regulation of lipid metabolism in liver (PPARα), adipose tissue (PPARγ), and skeletal muscle (PPARδ). This review provides an overview of the regulation of LD-associated proteins by PPARα, PPARδ, and PPARγ in adipose tissue, liver, macrophages, and skeletal muscle. It is concluded that many LD-associated proteins, including members of the PLIN family, CIDEC, CIDEA, HILPDA, FITM1, FITM2, and G0S2 are under direct transcriptional control of PPARs. Upregulation of LD-associated proteins by PPARs provides a mechanism to link uptake of lipids to regulation of lipid storage capacity. This article is part of a Special Issue entitled: Recent Advances in Lipid Droplet Biology edited by Rosalind Coleman and Matthijs Hesselink. [Display omitted] •Most cell types carry lipid droplets and lipid droplet-associated proteins.•PPARs are master regulators of lipid metabolism in various cell types.•The three PPARs differ in their ligand specificity and in their expression profile across tissues.•PPARs play a key role in the regulation of the expression of LD-associated proteins.•The expression level of LD-associated proteins and the regulation by PPARs is cell type specific.