Maternal High-Fat Diet Exaggerates Atherosclerosis in Adult Offspring by Augmenting Periaortic Adipose Tissue-Specific Proinflammatory Response
Maternal High-Fat Diet Exaggerates Atherosclerosis in Adult Offspring by Augmenting Periaortic Adipose Tissue-Specific Proinflammatory Response
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DOI：
10.1161/atvbaha.114.305122
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发表时间：
2015-03
期刊：
影响因子：
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通讯作者：
Noriyuki Wakana;Daisuke Irie;M. Kikai;Kensuke Terada;Keita Yamamoto;Hiroyuki Kawahito;Taku Kato;T. Ogata;T. Ueyama;S. Matoba;H. Yamada
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作者：
Noriyuki Wakana;Daisuke Irie;M. Kikai;Kensuke Terada;Keita Yamamoto;Hiroyuki Kawahito;Taku Kato;T. Ogata;T. Ueyama;S. Matoba;H. Yamada
目的：母体肥胖通过内脏脂肪组织的发育改变导致后代的代谢紊乱;然而，其对动脉粥样硬化形成的影响尚不清楚。血管周围脂肪组织最近被牵连在血管重塑和血管反应性。我们假设母体高脂饮食（HFD）暴露对血管周围脂肪组织的发育修饰促进了成年后代的动脉粥样硬化。方法和结果-在妊娠期和哺乳期给8周龄雌性载脂蛋白E缺陷小鼠喂食HFD或正常饮食（ND）。后代从8周龄开始喂食高胆固醇饮食。与ND喂养的母鼠（O-ND）相比，HFD喂养的母鼠（O-HFD）的20周龄雄性后代显示整个主动脉的动脉粥样硬化病变增加2.1倍。尽管O-HFD组附睾白色脂肪组织中白细胞介素-6、肿瘤坏死因子和单核细胞趋化蛋白-1的mRNA表达和巨噬细胞的积聚少于O-ND组，但O-HFD组胸主动脉周围脂肪组织（tPAT）显示出过度的炎症反应。与来自O-ND的tPAT相比，来自8周龄O-HFD的tPAT沿远端腹主动脉腹腔内移植加重了受体载脂蛋白E缺陷小鼠肾下主动脉的动脉粥样硬化发展（210%，P<0.01）。虽然在8周龄的tPAT中很少检测到巨噬细胞积聚，但巨噬细胞集落刺激因子的mRNA表达和蛋白水平在O-HFD中显著升高（分别为2.3倍、3.3倍，P<0.05），表明巨噬细胞集落刺激因子表达的增加有助于巨噬细胞积聚的增加，随后是促炎反应的增强。结论：我们的研究结果表明，母体HFD通过增加巨噬细胞集落刺激因子表达而增强tPAT特异性炎症反应，从而加剧后代动脉粥样硬化的发展。
Objective— Maternal obesity elicits offspring’s metabolic disorders via developmental modifications of visceral adipose tissue; however, its effect on atherogenesis remains undefined. Perivascular adipose tissue has recently been implicated in vascular remodeling and vasoreactivity. We hypothesize that developmental modifications of perivascular adipose tissue by maternal high-fat diet (HFD) exposure promotes atherosclerosis in adult offspring. Approach and Results— Eight-week-old female apolipoprotein E-deficient mice were fed an HFD or normal diet (ND) during gestation and lactation. Offspring were fed a high-cholesterol diet from 8 weeks of age. Twenty-week-old male offspring of HFD-fed dams (O-HFD) showed a 2.1-fold increase in atherosclerotic lesion of the entire aorta compared with those of ND-fed dams (O-ND). Although mRNA expressions of interleukin-6, tumor necrosis factor, and monocyte chemotactic protein-1 and accumulation of macrophages in epididymal white adipose tissue were less in O-HFD than in O-ND, thoracic periaortic adipose tissue (tPAT) showed an exaggerated inflammatory response in O-HFD. Intra-abdominal transplantation of tPAT from 8-week-old O-HFD alongside the distal abdominal aorta exaggerated atherosclerosis development of the infrarenal aorta in recipient apolipoprotein E-deficient mice compared with tPAT from O-ND (210%, P<0.01). Although macrophage accumulation was rarely detected in tPAT of 8-week-old offspring, mRNA expression and protein levels of macrophage colony–stimulating factor were markedly elevated in O-HFD (2.3-fold, 3.3-fold, respectively, P<0.05), suggesting that increased macrophage colony–stimulating factor expression contributes to the augmented accumulation of macrophages, followed by the enhanced proinflammatory response. Conclusions— Our findings demonstrate that maternal HFD exaggerates atherosclerosis development in offspring by augmenting tPAT-specific inflammatory response proceeded by an increased expression of macrophage colony–stimulating factor.