ARTD1 deletion causes increased hepatic lipid accumulation in mice fed a high-fat diet and impairs adipocyte function and differentiation
ARTD1 deletion causes increased hepatic lipid accumulation in mice fed a high-fat diet and impairs adipocyte function and differentiation
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DOI：
10.1096/fj.11-200212
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发表时间：
2012-06-01
期刊：
影响因子：
4.8
通讯作者：
Hottiger, Michael O.
中科院分区：
文献类型：
--
作者：
Erener, Sueheda;Mirsaidi, Ali;Hottiger, Michael O.
ADP-核糖基转移酶类白喉毒素1[ARTD1；以前称为多聚ADP-核糖聚合酶1(PARP1)]是一种染色质相关酶，参与调节代谢稳态。肝脏是葡萄糖和脂肪代谢的核心，受到肥胖和代谢综合征的严重影响。在这里，我们表明，当喂食高脂饮食(HFD)时，缺乏ARTD1的小鼠出现加剧的肝脏脂肪变性。ARTD1(-/-)小鼠的肝脏重量比野生型(WT)小鼠高19%，血清胆固醇浓度(38%)显著增加，糖耐量受损。此外，喂饲HFD的ARTD1(-/-)小鼠的脂肪细胞功能和大小显著减少(WT组7794亩m(2)，ARTD1(-/-)鼠5579亩m(2))。从ARTD1(-/-)小鼠分离的脂肪基质细胞(ASCs)的成脂分化显著降低(WT和ARTD1(-/-)ASCs中油红O阳性细胞的比例分别为28%和11%)，这表明脂肪生成障碍是这种脂肪组织功能障碍的根本原因。ARTD1的这种功能是脂肪形成所特有的，因为成骨分化不受ARTD1缺失的影响。综上所述，我们表明，喂食HFD的ARTD1(-/-)小鼠表现出脂肪生成受阻和肝脏脂肪变性加剧，这可能对非酒精性脂肪性肝病有重要影响。-Erener，S.，Mirsaidi，A.，Hesse，M.，Tiden，A.N.，Ellingsgaard，H.，Kostadinova，R.，Donath，M.Y.，Richards，P.J.，HotTiger，M.O.ARTD1缺失会导致喂食高脂饮食的小鼠肝脏脂肪堆积增加，并损害脂肪细胞的功能和分化。FASE B J.26,2631-2638(2012)。Www.fasebj.org
ADP-ribosyltransferase Diphtheria toxin-like 1 [ARTD1; formerly called poly-ADP-ribose polymerase 1 (PARP1)] is a chromatin-associated enzyme involved in regulating metabolic homeostasis. The liver is at the core of glucose and lipid metabolism and is significantly affected by obesity and the metabolic syndrome. Here, we show that when fed a high-fat diet (HFD), mice lacking ARTD1 developed exacerbated hepatic steatosis. ARTD1(-/-) mice had a 19% higher liver weight than wild-type (WT) animals and exhibited a significantly increased serum concentration of cholesterol (38%) and impaired glucose tolerance. In addition, adipocyte function and size were significantly reduced in ARTD1(-/-) mice fed an HFD (7794 mu m(2) for WT and 5579 mu m(2) for ARTD1(-/-) mice). The significantly reduced adipogenic differentiation of adipose-derived stromal cells (ASCs) isolated from ARTD1(-/-) mice (28 vs. 11% Oil red O-positive cells in WT and ARTD1(-/-) ASCs, respectively) suggested that impaired adipogenesis as the underlying cause for this adipose tissue malfunction. This function of ARTD1 was specific for adipogenesis, since osteogenic differentiation was not affected by the ARTD1 deletion. In summary, we show that ARTD1(-/-) mice fed an HFD display impaired adipogenesis and show exacerbated hepatic steatosis, which can have important implications for nonalcoholic fatty liver disease.-Erener, S., Mirsaidi, A., Hesse, M., Tiaden, A. N., Ellingsgaard, H., Kostadinova, R., Donath, M. Y., Richards, P. J., Hottiger, M. O. ARTD1 deletion causes increased hepatic lipid accumulation in mice fed a high-fat diet and impairs adipocyte function and differentiation. FASEB J. 26, 2631-2638 (2012). www.fasebj.org