Adipocyte-specific expression of C-type natriuretic peptide suppresses lipid metabolism and adipocyte hypertrophy in adipose tissues in mice fed high-fat diet.
Adipocyte-specific expression of C-type natriuretic peptide suppresses lipid metabolism and adipocyte hypertrophy in adipose tissues in mice fed high-fat diet.
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DOI：
10.1038/s41598-018-20469-z
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发表时间：
2018-02-01
影响因子：
4.6
通讯作者：
Kangawa K
中科院分区：
文献类型：
--
作者：
Bae CR;Hino J;Hosoda H;Son C;Makino H;Tokudome T;Tomita T;Hosoda K;Miyazato M;Kangawa K
c型利钠肽（CNP）表达于多种组织，包括脂肪和内皮，并通过结合和激活其受体鸟酰环化酶b发挥作用。我们最近发现，内皮细胞中CNP的过度表达可以保护小鼠免受高脂肪饮食（HFD）诱导的肥胖。考虑到肥胖期间内皮细胞的CNP影响脂肪组织，脂肪细胞中的CNP可能直接调节肥胖期间脂肪细胞的功能。因此，为了阐明CNP在脂肪细胞中的作用，我们评估了3T3-L1脂肪细胞和脂肪细胞特异性过表达CNP的转基因（Tg）小鼠（A-CNP）。我们发现CNP在3T3-L1脂肪细胞中激活cGMP-VASP通路。与Wt小鼠相比，A-CNP Tg小鼠在hfd诱导的肥胖过程中，脂肪重量和脂肪细胞肥大减少，脂肪酸β-氧化、脂解相关基因表达和能量消耗增加。这些作用导致肠系膜脂肪垫中巨噬细胞标志物F4/80水平降低，炎症减轻。此外，A-CNP Tg小鼠表现出改善的葡萄糖耐量和胰岛素敏感性，这与胰岛素刺激Akt磷酸化增强有关。我们的研究结果表明，脂肪细胞中CNP的过度表达可以防止脂肪细胞肥大、过度脂质代谢、炎症和胰岛素敏感性降低。
C-type natriuretic peptide (CNP) is expressed in diverse tissues, including adipose and endothelium, and exerts its effects by binding to and activating its receptor, guanylyl cyclase B. Natriuretic peptides regulate intracellular cGMP and phosphorylated vasodilator-stimulated phosphoprotein (VASP). We recently revealed that overexpression of CNP in endothelial cells protects against high-fat diet (HFD)-induced obesity in mice. Given that endothelial CNP affects adipose tissue during obesity, CNP in adipocytes might directly regulate adipocyte function during obesity. Therefore, to elucidate the effect of CNP in adipocytes, we assessed 3T3-L1 adipocytes and transgenic (Tg) mice that overexpressed CNP specifically in adipocytes (A-CNP). We found that CNP activates the cGMP–VASP pathway in 3T3-L1 adipocytes. Compared with Wt mice, A-CNP Tg mice showed decreases in fat weight and adipocyte hypertrophy and increases in fatty acid β-oxidation, lipolysis-related gene expression, and energy expenditure during HFD-induced obesity. These effects led to decreased levels of the macrophage marker F4/80 in the mesenteric fat pad and reduced inflammation. Furthermore, A-CNP Tg mice showed improved glucose tolerance and insulin sensitivity, which were associated with enhanced insulin-stimulated Akt phosphorylation. Our results suggest that CNP overexpression in adipocytes protects against adipocyte hypertrophy, excess lipid metabolism, inflammation, and decreased insulin sensitivity during HFD-induced obesity.
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影响因子：
4.5
作者：
Bakillah A;Hussain MM
通讯作者：
Hussain MM
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15.9
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Engeli, Stefan;Birkenfeld, Andreas L.;Moro, Cedric
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通讯作者：
Peters JC
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Roche, Helen M.