New wrinkles in lipoprotein lipase biology

Abstract

Purpose of review: We summarize recent progress on GPIHBP1, a molecule that transports lipoprotein lipase (LPL) to the capillary lumen, and discuss several newly studied molecules that appear important for the regulation of LPL activity.

Recent findings: LPL, the enzyme responsible for the lipolytic processing of triglyceride-rich lipoproteins, interacts with multiple proteins and is regulated at multiple levels. Several regulators of LPL activity have been known for years and have been investigated thoroughly, but several have been identified only recently, including an endothelial cell protein that transports LPL to the capillary lumen, a microRNA that reduces LPL transcript levels, a sorting protein that targets LPL for uptake and degradation, and a transcription factor that increases the expression of apolipoproteins that regulate LPL activity.

Summary: Proper regulation of LPL is important for controlling the delivery of lipid nutrients to tissues. Recent studies have identified GPIHBP1 as the molecule that transports LPL to the capillary lumen, and have also identified other molecules that are potentially important for regulating LPL activity. These new discoveries open new doors for understanding basic mechanisms of lipolysis and hyperlipidemia.

FIGURE 1

Mislocalization of LPL in tissues of Gpihbp1−/− mice. (a) Confocal microscopy showing the binding of GPIHBP1-specific antibodies, LPL-specific antibodies, and collagen IV-specific antibodies to brown adipose tissue (BAT) from wild-type and Gpihbp1−/− mice. Scale bars, 100 μm. (b, c) Confocal microscopy showing the binding of CD31-specific antibodies, LPL-specific antibodies, and β-dystroglycan-specific antibodies to heart (b) and skeletal muscle (c) of wild-type and Gpihbp1−/− mice. The scale bars show a distance of 100 μm (skeletal muscle) or 50 μm (heart). Reproduced with permission from [29^■■].

FIGURE 2

Absence of lipoprotein lipase from the capillary lumen of Gpihbp1−/− mice. Confocal microscopy showing the binding of CD31-specific antibodies, GPIHBP1-specific antibodies, and LPL-specific antibodies to brown adipose tissue (BAT) of a wild-type mouse and a Gpihbp1−/− mouse. Images were taken with a 100× objective without optical zoom or with 4× optical zoom. To visualize both the apical and basolateral surfaces of capillaries, cross-sections of capillaries containing an endothelial cell nucleus (blue) were identified (boxed areas) and viewed at high magnification. GPIHBP1 (purple), LPL (red), and CD31 (green) were detected at the apical and basolateral surfaces of endothelial cells in wild-type mice, but no LPL was present on the apical (luminal) surface of capillaries in Gpihbp1−/− mice. Scale bar, 2.5 μm. Reproduced with permission from [29^■■].