High-Fat Diet Promotes Macrophage-Mediated Hepatic Inflammation and Aggravates Diethylnitrosamine-Induced Hepatocarcinogenesis in Mice.
High-Fat Diet Promotes Macrophage-Mediated Hepatic Inflammation and Aggravates Diethylnitrosamine-Induced Hepatocarcinogenesis in Mice.
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高脂肪饮食促进巨噬细胞介导的肝脏炎症并加重二乙基亚硝胺诱导的肝癌发生
DOI：
10.3389/fnut.2020.585306
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发表时间：
2020
影响因子：
5
通讯作者：
Shou Q
中科院分区：
文献类型：
--
作者：
Fu H;Tang B;Lang J;Du Y;Cao B;Jin L;Fang M;Hu Z;Cheng C;Liu X;Shou Q
已有研究表明，饮食和营养在肝细胞癌的发生发展中起着重要作用。在这项研究中，我们研究了高脂饮食(HFD)对二乙基亚硝胺(DEN)诱导的小鼠肝癌形成的潜在促进作用机制。六味地黄汤显著降低DEN所致小鼠的存活率，并导致严重的肝功能障碍，表现为升高血清谷丙转氨酶、谷草转氨酶和碱性磷酸酶水平，增加肝指数、肝结节计数和γ-谷氨酰转移酶(γ-GT)活性。此外，与对照组相比，HFD组小鼠的肝脏中发现了更多的脂滴和肝细胞，其肝癌沟内和周围的胶原蛋白很少，并有大量的炎症细胞，如巨噬细胞。肝组织中增殖细胞核抗原、核因子-κB、细胞周期蛋白D1、肿瘤坏死因子和白介素1的表达显著增加。在体外，我们发现棕榈酸处理后巨噬细胞诱导型一氧化氮合酶(INOS)百分率增加，并分泌炎症因子和细胞因子，如白介素6(IL-6)、白介素10(IL-10)、CCL2、干扰素γ(干扰素γ)和肿瘤坏死因子。因此，我们的结果表明，HFD可能通过破坏肝功能，通过招募和极化肝脏中的巨噬细胞来增强炎症反应，从而促进DEN诱导的小鼠肝癌的发生。因此，这项研究可以为HFD在肝细胞癌中的促肿瘤作用提供新的见解。
It has been reported that diet and nutrition play important roles in the occurrence and development of hepatocellular carcinoma (HCC). In this study, we investigated the potential tumor-promoting mechanisms of a high-fat diet (HFD) in mice with dietondiethylnitrosamine (DEN)-induced hepatocarcinogenesis. HFD significantly decreased the survival rate and induced severe liver dysfunction in DEN-induced mice, as indicated by increased serum glutamic-pyruvic transaminase (ALT), glutamic oxalacetic transaminase (AST), and alkaline phosphatase (ALP) levels and increased liver index, liver nodule count, and γ-glutamyltransferase (γ-GT) activity. Moreover, an increased number of fat droplets and HCCs were found in the livers of the HFD mice, who displayed little collagen in and around the liver cancer groove and the infiltration of large number of inflammatory cells, such as macrophages, compared with the control mice. HFD also significantly increased proliferating cell nuclear antigen (PCNA), nuclear factor-κB (NF-κB), cyclin D1, tumor necrosis factor (TNF), and interleukin-1 (IL-1) expression levels in the liver. In vitro, we found that the inducible nitric oxide synthase (iNOS) percentage increased in macrophages after palmitic acid treatment, as well as the secretion of inflammatory factors and cytokines such as interleukin-6(IL-6), interleukin-10(IL-10), CCL2, Interferon γ (IFN-γ), and TNF. Thus, our results demonstrate that an HFD may promote DEN-induced hepatocarcinogenesis in mice by destroying liver function and enhancing the inflammatory response by recruiting and polarizing macrophages in the liver. This study could therefore provide new insights into the tumor promoting effects of an HFD in HCC.
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影响因子：
--
作者：
Zhang, Xia;Goncalves, Ricardo;Mosser, David M
通讯作者：
Mosser, David M
影响因子：
0.2
作者：
Poosarla, Chandrashekar;Ramesh, Maya;Sundar, Mural
通讯作者：
Sundar, Mural
DOI：
10.1165/rcmb.2013-0386oc
发表时间：
2014-04-01
影响因子：
6.4
作者：
Redente, Elizabeth F.;Keith, Rebecca C.;Riches, David W. H.
通讯作者：
Riches, David W. H.
影响因子：
5.6
作者：
Memon, Azra;Pyao, Yuliya;Lee, Woon Kyu
通讯作者：
Lee, Woon Kyu
影响因子：
56.9
作者：
Flaherty, Stephen E., III;Grijalva, Ambar;Ferrante, Anthony W., Jr.
通讯作者：
Ferrante, Anthony W., Jr.