Mesenteric adipose tissue contributes to intestinal barrier integrity and protects against nonalcoholic fatty liver disease in mice.
Mesenteric adipose tissue contributes to intestinal barrier integrity and protects against nonalcoholic fatty liver disease in mice.
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肠系膜脂肪组织有助于维持肠道屏障的完整性并预防小鼠非酒精性脂肪肝。
DOI：
10.1152/ajpgi.00079.2018
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发表时间：
2018-11
期刊：
影响因子：
--
通讯作者：
Liu Yulan
中科院分区：
文献类型：
--
作者：
Wu Zhe;Tan Jiang;Chi Yujing;Zhang Feng;Xu Jun;Song Yang;Cong Xu;Wu Na;Liu Yulan
内脏脂肪组织（VAT）与非酒精性脂肪性肝病（NAFLD）有关。然而，肠系膜脂肪组织（MAT），VAT的一部分，在NAFLD中的作用尚不清楚。在本研究中，我们监测了肝脏和四个仓库的增值税在高脂肪饮食（HFD）喂养的小鼠在多个时间点（4，8和12周）。MAT在HFD喂养的第八周时已经发炎，早于其他VAT仓库。此外，在HFD 8周后去除MAT导致更严重的脂肪变性和更多的炎症浸润灶，以及更高的NAFLD活动评分。与这些发现一致，在发炎的MAT去除小鼠的肝脏中促炎细胞因子和脂质拮抗剂基因的mRNA表达增加。MAT的去除也损伤了肠道屏障并促进了肠道炎症。还在发炎的MAT去除小鼠中评价了转移到肝脏的细菌负荷和脂多糖的循环水平。在涉及脂肪细胞和肠上皮细胞的共培养实验中，CT-26细胞中闭合小带-1（ZO-1）和闭合蛋白的mRNA表达上调，单层Caco-2细胞的通透性在脂肪细胞或发炎的脂肪细胞的刺激下升高。综上所述，这些结果表明，MAT去除损伤肠屏障并加重NAFLD，MAT炎症可能是通过维持肠屏障保护肝脏的代偿反应。肠系膜脂肪组织（MAT）位于肠道和肝脏之间，在肝脏代谢疾病中起着关键作用。在目前的研究中，我们发现MAT在高脂肪饮食喂养的小鼠中容易发生炎症。去除发炎的MAT导致更多的肝脏炎症、脂质积聚和葡萄糖耐量降低。此外，我们发现MAT有助于肠道屏障的完整性，从而阐明了为什么MAT去除会加重非酒精性脂肪肝。
Visceral adipose tissue (VAT) is related to nonalcoholic fatty liver disease (NAFLD). However, the role of mesenteric adipose tissue (MAT), part of the VAT, in NAFLD is unclear. In the present study, we monitored the liver and four depots of the VAT in high-fat diet (HFD)-feeding mice at multiple time points (4, 8, and 12 wk). The MAT had become inflamed by the eighth week of HFD feeding, earlier than other depots of VAT. Furthermore, MAT removal after 8 wk of HFD resulted in more severe steatosis and more foci of inflammation infiltration, as well as higher NAFLD activity scores. Consistent with these findings, the mRNA expression of proinflammatory cytokines and lipid anabolism genes was increased in the livers of inflamed MAT-removal mice. MAT removal also injured the intestinal barrier and promoted intestinal inflammation. The bacterial load translocated to the liver and circulating levels of lipopolysaccharide were also evaluated in inflamed MAT-removal mice. In a coculture experiment involving adipocytes and intestinal epithelial cells, mRNA expression of zonula occludens-1 (ZO-1), and occludin in CT-26 cells was upregulated and permeability of monolayer Caco-2 cells was elevated under stimulation from adipocytes or inflamed adipocytes. Taken together, these results demonstrated that MAT removal damaged the intestinal barrier and aggravated NAFLD and that MAT inflammation may be a compensatory response to protect the liver by maintaining the intestinal barrier. NEW & NOTEWORTHY The mesenteric adipose tissue (MAT) lies between the gut and liver and plays a critical role in hepatic metabolic diseases. In the present study, we found that the MAT was prone to inflammation in high-fat diet-fed mice. Removal of the inflamed MAT resulted in more hepatic inflammation, lipid accumulation, and decreased glucose tolerance. Furthermore, we showed that the MAT contributed to intestinal barrier integrity, thus clarifying why MAT removal aggravated nonalcoholic fatty liver disease.
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影响因子：
7.7
作者：
Catalano KJ;Stefanovski D;Bergman RN
通讯作者：
Bergman RN
影响因子：
7.7
作者：
S. Wueest;Flurin Item;Fabrizio C. Lucchini;T. D. Challa;Werner Müller-;M. Blüher;D. Konrad
通讯作者：
S. Wueest;Flurin Item;Fabrizio C. Lucchini;T. D. Challa;Werner Müller-;M. Blüher;D. Konrad
影响因子：
3.7
作者：
Caesar R;Manieri M;Kelder T;Boekschoten M;Evelo C;Müller M;Kooistra T;Cinti S;Kleemann R;Drevon CA
通讯作者：
Drevon CA
影响因子：
11.1
作者：
Amar, Jacques;Chabo, Chantal;Waget, Aurelie;Klopp, Pascale;Vachoux, Christelle;Bermudez-Humaran, Luis G.;Smirnova, Natalia;Berge, Mathieu;Sulpice, Thierry;Lahtinen, Sampo;Ouwehand, Arthur;Langella, Philippe;Rautonen, Nina;Sansonetti, Philippe J.;Burcelin, Remy
通讯作者：
Burcelin, Remy
影响因子：
9.8
作者：
Li, Hong;Lelliott, Christopher;Michaelsson, Erik
通讯作者：
Michaelsson, Erik