Lipoprotein lipase: the regulation of tissue specific... : Current Opinion in Lipidology (original) (raw)

Atherosclerosis: cell biology and lipoproteins

Lipoprotein lipase: the regulation of tissue specific expression and its role in lipid and energy metabolism

Preiss-Landl, Karina; Zimmermann, Robert; Hämmerle, Günter; Zechner, Rudolf

SFB-Biomembranes Research Center, Institute of Molecular Biology, Biochemistry and Microbiology, Karl-Franzens-University, Graz, Austria

Correspondence to Rudolf Zechner, Institute of Molecular Biology, Biochemistry and Microbiology, Karl-Franzens-University, Graz, Heinrichstrasse 31a, A-8010 Graz, Austria. Tel: +43 316 380 1900; fax: +43 316 380 9016; e-mail: [email protected]

Abbreviations

ADD-1: adipocyte differentiation and determination factor

ABCA1: ATP binding casette transporter A1

COUP-TF: chicken ovalbumin upstream promoter transcriptional factor

FFA: free fatty acid

LPL: lipoprotein lipase

LXR: oxysterol liver X receptor

PPAR: peroxisome proliferator-activated receptor

PPRE: PPAR responsive element

RXR: rexinoid receptor

SMRT: silencing mediator of the retinoic acid receptor and thyroid receptor

SRE: sterol regulatory element

SREBP: sterol regulatory element binding protein

TNFα: tumor necrosis factorα

VLDL: very low-density lipoprotein

Abstract

Purpose of review

The aim of this review is to summarize and discuss recent advances in the understanding of the physiological role of lipoprotein lipase in lipid and energy metabolism.

Recent findings

Studies on the transcriptional and the posttranscriptional level of lipoprotein lipase expression have provided new insights into the complex mechanisms that are involved in the regulation of the enzyme. Additionally a large body of evidence from both human studies and animal models suggests that the level of lipoprotein lipase expression in a given tissue is the rate limiting process for the uptake of triglyceride derived fatty acids. Imbalances in the partitioning of fatty acids among peripheral tissues have major metabolic consequences. For example, in mice both decreased lipoprotein lipase activities in adipose tissue and increased activity in muscle are associated with resistance to obesity; lack of lipoprotein lipase activity in macrophages is correlated with a decreased susceptibility to develop atherosclerotic lesions and overexpression of the enzyme in muscle is associated with increased blood glucose levels and insulin resistance.

Summary

Considering the central role of lipoprotein lipase in energy metabolism it is a reasonable goal to discover and develop new drugs that affect the tissue specific expression pattern of the enzyme.