Isoproterenol increases active lipoprotein lipase in adipocyte medium and in rat plasma Xavier Ballart, Mariona Siches, Julia Peinado-Onsurbe, Dolores López-Tejero, Miquel Llobera, Ignasi Ramírez, Monique Q. Robert * Departament de Bioquímica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona, Diagonal 645, 08028 Barcelona, Spain Received 27 May 2003; accepted 5 September 2003 Abstract White adipose tissue (WAT) lipoprotein lipase (LPL) activity channels diet fat towards storage in adipocytes.Adrenaline (ADR) is accepted to reduce WAT or adipocyte LPL activity (LPLa), but available data are not clear-cut regarding long exposure toADR in vitro or in vivo. We studied the effects of long exposures to ADR or b-adrenergic agonist on LPL: in isolated rat adipocytes (3 h) and in rats (>1 day). Isoproterenol (ISO) (1 μM) did not alter LPLmRNA nor LPLa in adipocytes, but increased LPLa in medium more than twofold (3.58 ± 0.35 vs. 1.32 ± 0.35 mU/10 6 adipocytes, P < 0.001). Effect was time (not present at 1 h, clear at 2 h) and concentration dependent (high sensitivity from 10 to 100 nM, max at 1 μM). Adenylate cyclase activator or cyclic AMP (cAMP) analogue produced a similar increase. Thus in adipocytes ISO produced an increase in LPLa release and/or a decrease in extracellular LPLa degradation. ADR or ISO treated rats had a two to fourfold decrease inWAT LPLa vs. unchanged LPLmRNA. This decrease was 10-fold inWAT heparin-releasable LPLa (5.7 ± 0.6 vs. 57.3 ± 10.2 mU/g, P < 0.001), which represents peri/extracellular LPLa. Plasma LPLa was increased 11-fold by ADR (3.30 ± 0.58 vs. 0.32 ± 0.08 mU/ml, P < 0.001) whereas only threefold by ISO (P > 0.01). We suggest that in vivo ADR increased release of active LPL to plasma from endothelial cells of LPL-rich tissue(s)—WAT was probably one of these tissues releasing LPL since it lost 90% of its peri/extracellular LPLa—and/or decreased degradation of plasma active LPL. Since liver LPLa was not increased, plasma active LPL might be kept away from hepatic degradation by binding to stabilising entities in plasma (fatty acids (FA), lipoproteins or soluble heparan sulphates (HS)). In conclusion, we believe this is the first report stating that: (a) ISO increases LPLa in isolated adipocyte medium, and (b) ADR administration to rats decreases WAT extracellular active LPL and increases preheparin plasma active LPL. © 2003 Éditions scientifiques et médicales Elsevier SAS. All rights reserved. Keywords: Adrenaline; White adipose tissue; Preheparin plasma; Cyclic AMP; Heparan sulphate proteoglycans 1. Introduction Lipoprotein lipase (LPL) is the main enzyme responsible for the hydrolysis of circulating triacylglycerols (TAG) and, thus, provides fatty acids (FA) to LPL-rich tissues. Both plasma TAG-rich lipoproteins (chylomicrons and very low density lipoproteins (VLDL)) are LPL substrates. Both con- tain the TAG substrate in their hydrophobic core and apoli- poprotein C-II (apo C-II, the serum cofactor for LPL cata- lytic activity) on their surface. Of the total LPL activity (LPLa) in the body most is located in skeletal muscle and white adipose tissue (WAT).This is due to the high percent- age of body weight these tissues represent, and forWAT to high LPLa per g tissue. LPL inWAT channels plasma TAG (from dietary TAG or from hepatic synthesis) towards stor- age in adipocytes. LPL in muscle supplies fuel for oxidation and ATP synthesis in a tissue with a high-energy demand. Functional LPL is a homodimer located on the luminal side of endothelial cells lining capillaries and larger vessels. It is most abundant on capillary walls in LPL-rich tissues [1]. Cells responsible for LPL synthesis are parenchymal cells in tissue [2]. In these cells, LPL is found in its active dimeric form in the endoplasmic reticulum and Golgi compartments [3], before it is secreted in its mature glycosylated form and transported to its functional site at capillary. Mechanisms involved in extracellular transport to endothelial cells are largely unknown. Movement from subendothelial side to luminal side of endothelial cells is by transcytosis. LPL is bound to the cell surface of endothelial or LPL-synthesising * Corresponding author. Tel.: +34-93-403-4602; fax: +34-93-402-1559. E-mail address: mrobert@porthos.bio.ub.es (M.Q. Robert). Biochimie 85 (2003) 971–982 www.elsevier.com/locate/biochi © 2003 Éditions scientifiques et médicales Elsevier SAS. All rights reserved. doi:10.1016/j.biochi.2003.09.001