Ballart Xavier, Siches Mariona, Peinado-Onsurbe Julia, López-Tejero Dolores, Llobera Miquel, Ramírez Ignasi, Robert Monique Q
Departament de Bioquímica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona, Diagonal 645, 08028 Barcelona, Spain.
Biochimie. 2003 Oct;85(10):971-82. doi: 10.1016/j.biochi.2003.09.001.
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 to ADR in vitro or in vivo. We studied the effects of long exposures to ADR or beta-adrenergic agonist on LPL: in isolated rat adipocytes (3 h) and in rats (>1 day). Isoproterenol (ISO) (1 microM) 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 microM). 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 in WAT LPLa vs. unchanged LPLmRNA. This decrease was 10-fold in WAT 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.
白色脂肪组织（WAT）中的脂蛋白脂肪酶（LPL）活性可促使膳食脂肪储存于脂肪细胞中。肾上腺素（ADR）被认为可降低WAT或脂肪细胞的LPL活性（LPLa），但关于其在体外或体内长时间暴露的现有数据并不明确。我们研究了长时间暴露于ADR或β-肾上腺素能激动剂对LPL的影响：在分离的大鼠脂肪细胞中（3小时）以及在大鼠体内（>1天）。异丙肾上腺素（ISO）（1微摩尔）并未改变脂肪细胞中的LPLmRNA或LPLa，但使培养基中的LPLa增加了两倍多（3.58±0.35对1.32±0.35毫单位/10⁶个脂肪细胞，P<0.001）。该效应具有时间依赖性（1小时时不存在，2小时时明显）和浓度依赖性（10至100纳摩尔具有高敏感性，1微摩尔时达到最大值）。腺苷酸环化酶激活剂或环磷酸腺苷（cAMP）类似物产生了类似的增加。因此，在脂肪细胞中，ISO导致LPLa释放增加和/或细胞外LPLa降解减少。与LPLmRNA未改变相比，ADR或ISO处理的大鼠WAT中的LPLa降低了两到四倍。WAT中肝素可释放的LPLa降低了10倍（5.7±0.6对57.3±10.2毫单位/克，P<0.001），这代表了细胞周/细胞外LPLa。ADR使血浆LPLa增加了11倍（3.30±0.58对0.32±0.08毫单位/毫升，P<0.001），而ISO仅使其增加了三倍（P>0.01）。我们认为，在体内，ADR增加了富含LPL组织的内皮细胞向血浆中释放活性LPL——WAT可能是释放LPL的组织之一，因为它失去了90%的细胞周/细胞外LPLa——和/或减少了血浆活性LPL的降解。由于肝脏LPLa未增加，血浆活性LPL可能通过与血浆中的稳定实体（脂肪酸（FA）、脂蛋白或可溶性硫酸乙酰肝素（HS））结合而避免被肝脏降解。总之，我们相信这是第一份表明：（a）ISO增加分离的脂肪细胞培养基中的LPLa，以及（b）给大鼠注射ADR会降低WAT细胞外活性LPL并增加肝素前血浆活性LPL的报告。
