Localization of lipoprotein lipase and GPIHBP1 in mouse pancreas: effects of diet and leptin deficiency

In the exocrine pancreas LPL was found in capillaries, and was mostly co-localized with GPIHBP1. LPL was releasable by heparin, indicating localization on cell surfaces. Within the islets, most of the LPL was associated with beta cells and could not be released by heparin, indicating that the enzyme remained mostly within cells. Staining for LPL was found also in the glucagon-producing alpha cells, both in embryos (E18) and in adult mice. Only small amounts of LPL were found together with GPIHBP1 within the capillaries of islets. Neither a high fat diet nor fasting/re-feeding markedly altered the distribution pattern of LPL or GPIHBP1 in mouse pancreas. Islets from ob/ob mice appeared completely deficient of LPL in the beta cells, while LPL-staining was normal in alpha cells and in the exocrine pancreas. Leptin treatment of ob/ob mice for 12 days reversed this pattern, so that most of the islets expressed LPL in beta cells.We conclude that both LPL and GPIHBP1 are present in mouse pancreas, and that LPL expression in beta cells is dependent on leptin.Lipoprotein lipase (LPL) is responsible for the hydrolysis of triglycerides in plasma lipoproteins, generating fatty acids and monoglycerides for uptake in tissues and use in metabolic processes [1,2]. LPL is synthesized and secreted by parenchymal cells such as adipocytes and myocytes, but the enzyme acts at the luminal face of endothelial cells in capillaries where it is anchored to the plasma membrane in a heparin-releasable manner. The mechanism by which LPL is transported from the interstitial spaces surrounding parenchymal cells into capillaries involves an endothelial cell protein, glycosylphosphatidylinositol-anchored high density lipoprotein binding protein 1 (GPIHBP1), that binds LPL at the basolateral surface of capillaries and transports it into the capillary lumen [3]. In the absence of GPIHBP1, LPL is mislocalized to the subendothelial spaces, resulting in severe hypertriglyceridemia [4]. Two structural mo