NLRP3 deficiency did not attenuate NASH development under high fat calorie diet plus high fructose and glucose in drinking water
NLRP3 deficiency did not attenuate NASH development under high fat calorie diet plus high fructose and glucose in drinking water
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在高脂肪热量饮食加上高果糖和高葡萄糖饮用水下，NLRP3 缺乏并没有减弱 NASH 的发展
DOI：
10.1038/s41374-021-00535-3
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发表时间：
2021-02
影响因子：
5
通讯作者：
Jian Wu
中科院分区：
文献类型：
--
作者：
Liu-Yan Zhu;Chang Liu;Zong-Rui Li;Chen Niu;Jian Wu
背景：点状受体蛋白3（NLRP3）在非酒精性脂肪肝（NAFL）对非酒精性脂肪性肝炎进展过程中的炎症反应中起促进作用。通过废除其在小鼠中的表达：使用高脂肪卡路里饮食以及高果糖和饮用水中的葡萄糖（HFCD-HF/g）在野生型（WT）和NLRP3敲除（KO）中建立NASH（KO）小鼠。肝细胞损伤，肝脏脂肪变性和纤维化，以及肝脏的炎症反应和胰岛素抵抗，并确定肝脏重量，肝脏体重和肝透明质triglyceride triglyceride triglyceride triglyceride triglyceride triglyceride Triglyceride triglyceride triglyceride triglyceride triglyceride triglyceride triglyceride triglyceride triglyceride triglyceride triglyceride triglyceride triglyceride triglyceride累积的结果与HFCD-HF/G喂养下的WT小鼠相比，在NLRP3 - / - 小鼠中观察到胶原蛋白的沉积和严重的全身性胰岛素抵抗。与HFCD-HF/G-FED NLRP3 - / - 小鼠相比，MCP-1）和诱导一氧化氮合酶阳性（Inos+）M1巨噬细胞的浸润也得到了记录，在控制饮食下，NLRP3 - / - 小鼠的肝脏中，TNF-α和MCP-1的转录增加了iNOS+ M1巨噬细胞。 NASH的恶劣程度可能归因于NLRP3 - / - 小鼠中的肝脏MCP-1表达和M1巨噬细胞的浸润。
Background: NOD-like receptor protein 3 (NLRP3) plays a promoting role in the mediation of inflammatory response during progression of nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH). This study aimed to further delineate the role of NLRP3 in NASH development by abolishing its expression in mice. Methods: A high fat calorie diet plus high fructose and glucose in drinking water (HFCD-HF/G) was used to establish NASH in both wild-type (WT) and NLRP3 knock-out (KO) mice. Hepatocellular injury, hepatic steatosis and fibrosis, as well as inflammatory response and insulin resistance in the liver and epidydimal white adipose tissue (eWAT) were determined. Results: Elevated body weight, liver weight and serum alanine transaminase level, increased hepatic triglyceride accumulation and collagen deposition, and worsened systemic insulin resistance were observed in Nlrp3-/- mice compared to WT mice under HFCD-HF/G feeding. Upregulated hepatic transcription of tumor necrosis factor-α (TNF-α) and monocyte chemotactic protein-1 (MCP-1), and enhanced infiltration of inducible nitric oxide synthase-positive (iNOS+) M1 macrophages were also documented in HFCD-HF/G-fed Nlrp3-/- mice in comparison to HFCD-HF/G-fed WT mice. Moreover, transcription of TNF-α and MCP-1 and infiltration of iNOS+ M1 macrophages were increased in the liver of Nlrp3-/- mice under control diet. Conclusion: NLRP3 deficiency did not attenuate but aggravate NASH development under HFCD-HF/G feeding. The worsened extent of NASH might be attributed to enhanced hepatic MCP-1 expression and M1 macrophage infiltration in Nlrp3-/- mice. Our study points to additional caution when NLRP3 blockade is considered as a therapeutic strategy in the treatment of human NASH.
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影响因子：
25.7
作者：
Gaul S;Leszczynska A;Alegre F;Kaufmann B;Johnson CD;Adams LA;Wree A;Damm G;Seehofer D;Calvente CJ;Povero D;Kisseleva T;Eguchi A;McGeough MD;Hoffman HM;Pelegrin P;Laufs U;Feldstein AE
通讯作者：
Feldstein AE
影响因子：
7.7
作者：
Morinaga H;Mayoral R;Heinrichsdorff J;Osborn O;Franck N;Hah N;Walenta E;Bandyopadhyay G;Pessentheiner AR;Chi TJ;Chung H;Bogner-Strauss JG;Evans RM;Olefsky JM;Oh DY
通讯作者：
Oh DY
影响因子：
13.5
作者：
Wree, Alexander;Eguchi, Akiko;McGeough, Matthew D.;Pena, Carla A.;Johnson, Casey D.;Canbay, Ali;Hoffman, Hal M.;Feldstein, Ariel E.
通讯作者：
Feldstein, Ariel E.
影响因子：
64.5
作者：
Manning BD;Toker A
通讯作者：
Toker A
影响因子：
3.2
作者：
Ino, H
通讯作者：
Ino, H