Adipogenic human adenovirus-36 reduces leptin expression and secretion and increases glucose uptake by fat cells
Adipogenic human adenovirus-36 reduces leptin expression and secretion and increases glucose uptake by fat cells
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DOI：
10.1038/sj.ijo.0803366
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发表时间：
2007-01-01
影响因子：
4.9
通讯作者：
Dhurandhar, N. V.
中科院分区：
文献类型：
--
作者：
Vangipuram, S. D.;Yu, M.;Dhurandhar, N. V.
目的：人腺病毒Ad-36在动物模型中引起肥胖，并增强人和3T3-L1前脂肪细胞的分化和脂质积累，这可能部分解释了Ad-36的成脂作用。我们确定了Ad-36感染对脂肪细胞中瘦素和葡萄糖代谢的影响。设计：采用3T3-L1前脂肪细胞检测人腺病毒Ad-36、Ad-2、Ad-9和Ad-37感染后对瘦素分泌和脂质积累的影响。采用大鼠原代脂肪细胞，研究Ad-36感染对体外瘦素分泌和葡萄糖摄取的影响。此外，我们还比较了Ad- 36对感染和未感染Ad- 36的对照大鼠内脏脂肪组织中瘦素和新生脂肪生成途径相关基因表达的影响。结果：Ad-36在感染后第3天和第5天分别抑制3T3-L1细胞中瘦素mRNA的表达约58%和52%。在Ad- 36感染的3T3-L1细胞中，瘦素释放按细胞脂质含量标准化降低51% （P < 0.002）。感染了其他人腺病毒Ad- 9、Ad- 36或Ad-37的3T3-L1细胞的脂质积累明显增加，瘦素分泌明显减少。而人腺病毒Ad- 2不影响细胞脂质积累和瘦素释放。在大鼠原代脂肪细胞中，当胰岛素浓度为0.48 nM （P < 0.01）或1.6 nM （P < 0.05）时，Ad- 36使瘦素释放减少约40%，而当胰岛素浓度为0 nM或0.48 nM时，Ad- 36使葡萄糖摄取分别增加93% （P < 0.001）或18% （P < 0.05）。接下来，与未感染的体重和肥胖匹配的对照组相比，感染Ad- 36的大鼠的脂肪组织显示瘦素mRNA表达低2至5倍，乙酰辅酶a羧化酶-1表达高1.6至21倍，脂肪酸合成酶表达高1.2至6.3倍，这是重新生成脂肪的关键基因。结论：体外和离体研究表明，Ad- 36调节脂肪细胞分化、瘦素产生和糖代谢。在Ad- 36感染的动物或人类中，这种调节是否有助于增强脂肪形成和随之而来的肥胖需要确定。
Objective: Human adenovirus Ad-36 causes adiposity in animal models and enhances differentiation and lipid accumulation in human and 3T3-L1 preadipocytes, which may, in part, explain the adipogenic effect of Ad-36. We determined the consequences of Ad-36 infection on leptin and glucose metabolism in fat cells.Design: 3T3-L1 preadipocytes were used to determine the effect of infection by human adenoviruses Ad-36, Ad-2, Ad-9 and Ad-37 on leptin secretion and lipid accumulation. Rat primary adipocytes were used to determine the effect of Ad-36 infection on leptin secretion and glucose uptake in vitro. Furthermore, the effect of Ad- 36 on expressions of leptin and selected genes of de novo lipogenesis pathway of visceral adipose tissue were compared ex vivo, between Ad- 36 infected and uninfected control rats.Results: Ad-36 suppressed the expression of leptin mRNA in 3T3-L1 cells by approximately 58 and 52% on days 3 and 5 postinfection, respectively. Leptin release normalized to cellular lipid content was 51% lower ( P < 0.002) in the Ad- 36 infected 3T3-L1 cells. Lipid accumulation was significantly greater and leptin secretion was lower for the 3T3-L1 cells infected with other human adenoviruses Ad- 9, Ad- 36, or Ad-37. Whereas, human adenovirus Ad- 2 did not influence cellular lipid accumulation or the leptin release. In rat primary adipocytes, Ad- 36 reduced leptin release by about 40% in presence of 0.48 ( P < 0.01) or 1.6 nM insulin ( P < 0.05) and increased glucose uptake by 93% ( P < 0.001) or 18% ( P < 0.05) in presence of 0 or 0.48 nM insulin, respectively. Next, the adipose tissue of Ad- 36 infected rats showed two to fivefold lower leptin mRNA expression, and 1.6- to 21-fold greater expressions for acetyl Co-A carboxylase-1 and 1.2- to 6.3-fold greater expressions for fatty acid synthase, key genes of de novo lipogenesis, compared to the uninfected weight and adiposity matched controls.Conclusion: The in vitro and ex vivo studies show that Ad- 36 modulates adipocyte differentiation, leptin production and glucose metabolism. Whether such a modulation contributes to enhanced adipogenesis and consequent adiposity in Ad- 36 infected animals or humans needs to be determined.