GPIHBP1, a GPI-anchored protein required for the lipolytic processing of triglyceride-rich lipoproteins

Abstract

GPIHBP1, a small glycosylphosphatidylinositol-anchored glycoprotein, is required for the lipolytic processing of triglyceride-rich lipoproteins. GPIHBP1 knockout mice exhibit chylomicronemia, even on a low-fat diet, with plasma triglyceride levels of 3,500-5,000 mg/dl. GPIHBP1 is expressed highly in heart, adipose tissue, and skeletal muscle, the same tissues that express high levels of lipoprotein lipase (LPL). In each of these tissues, GPIHBP1 is located in capillary endothelial cells. Chinese hamster ovary (CHO) cells transfected with a GPIHBP1 expression vector bind LPL and chylomicrons avidly. The expression of GPIHBP1 in mice is modulated by fasting and refeeding and is also regulated by peroxisome proliferator-activated receptor (PPAR)gamma agonists. Here, we review recent progress in understanding GPIHBP1 and discuss its role in lipolysis.

Fig. 1.

Model of GPIHBP1 structure depicting a highly acidic N-terminal domain (yellow), a cysteine-rich lymphocyte antigen 6 (Ly6) domain (green), and a glycosylphosphatidylinositol (GPI)-anchor (deep purple) that tethers GPIHBP1 to the plasma membrane.

Fig. 2.

GPIHBP1 is expressed within the lumen of the capillaries of the mouse heart. Reproduced, with permission, from Beigneux et al. (9).

Fig. 3.

Lipoprotein lipase (LPL) binds to GPIHBP1 on the surface of transfected pgsA745 Chinese hamster ovary (CHO) cells. A: Binding of LPL (mean ± SD) to mouse GPIHBP1-expressing cells before and after treatment with PIPLC. Reproduced, with permission, from Beigneux et al. (9). B: Binding of human LPL to human GPIHBP1 on pgsA745 CHO cells. Only trace amounts of LPL bound to nontransfected cells. LPL did not bind to GPIHBP1 in which its Ly6 domain was replaced with the Ly6 domain of CD59. Reproduced, with permission, from Gin et al. (23).