Xia Zhunan, Stanhope Kimber L, Digitale Erin, Simion Oana-Maria, Chen Lanying, Havel Peter, Cianflone Katherine
Mike Rosenbloom Laboratory for Cardiovascular Research, McGill University Health Centre, Montreal H3A 1A1, Canada.
J Biol Chem. 2004 Feb 6;279(6):4051-7. doi: 10.1074/jbc.M311319200. Epub 2003 Nov 13.
Acylation-stimulating protein (ASP) acts as a paracrine signal to increase triglyceride synthesis in adipocytes. In mice, C3 (the precursor to ASP) knock-out (KO) results in ASP deficiency and leads to reduced body fat and leptin levels yet they are hyperphagic. In the present study, we investigated the mechanism for this energy repartitioning. Compared with wild-type (WT) mice, male and female C3(-/-) ASP-deficient mice had elevated oxygen consumption (VO2) in both the active (dark) and resting (light) phases of the diurnal cycle: +8.9% males (p < 0.05) +9.4% females (p < 0.05). Increased physical activity (movement) was observed during the dark phase in female but not in male KO animals. Female WT mice moved 16.9 +/- 2.4 m whereas KO mice moved 30.1 +/- 5.4 m, over 12 h, +78.4%, p < 0.05). In contrast, there was no difference in physical activity in male mice, but a repartitioning of dietary fat following intragastric fat administration was noted. This was reflected by increased fatty acid oxidation in liver and muscle in KO mice, with increased UCP2 (inguinal fat) and UCP3 (muscle) mRNA expression (p = 0.005 and 0.036, respectively). Fatty acid uptake into brown adipose tissue (BAT) and white adipose tissue (WAT) was reduced as reflected by a decrease in the fatty acid incorporation into lipids (BAT -68%, WAT -29%. The decrease of FA incorporation was normalized by intraperitoneal administration of ASP at the time of oral fat administration. These results suggest that ASP deficiency results in energy repartitioning through different mechanisms in male and female mice.
酰化刺激蛋白（ASP）作为一种旁分泌信号，可增加脂肪细胞中甘油三酯的合成。在小鼠中，C3（ASP的前体）基因敲除（KO）导致ASP缺乏，并导致体脂和瘦素水平降低，但它们食欲亢进。在本研究中，我们调查了这种能量重新分配的机制。与野生型（WT）小鼠相比，雄性和雌性C3（-/-）ASP缺陷小鼠在昼夜周期的活跃（黑暗）和休息（光照）阶段的耗氧量（VO2）均升高：雄性升高8.9%（p < 0.05），雌性升高9.4%（p < 0.05）。在黑暗阶段，雌性KO动物的身体活动（运动量）增加，而雄性则未增加。雌性WT小鼠在12小时内移动了16.9±2.4米，而KO小鼠移动了30.1±5.4米，增加了78.4%，p < 0.05）。相比之下，雄性小鼠的身体活动没有差异，但在胃内给予脂肪后，饮食脂肪的分配发生了重新分配。这表现为KO小鼠肝脏和肌肉中的脂肪酸氧化增加，UCP2（腹股沟脂肪）和UCP3（肌肉）mRNA表达增加（分别为p = 0.005和0.036）。棕色脂肪组织（BAT）和白色脂肪组织（WAT）对脂肪酸的摄取减少，这表现为脂肪酸掺入脂质的减少（BAT减少68%，WAT减少29%）。在口服脂肪时腹腔注射ASP可使脂肪酸掺入的减少恢复正常。这些结果表明，ASP缺乏通过不同机制导致雄性和雌性小鼠的能量重新分配。
