DSS-induced colitis is associated with adipose tissue dysfunction and disrupted hepatic lipid metabolism leading to hepatosteatosis and dyslipidemia in mice.
DSS-induced colitis is associated with adipose tissue dysfunction and disrupted hepatic lipid metabolism leading to hepatosteatosis and dyslipidemia in mice.
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DOI：
10.1038/s41598-021-84761-1
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发表时间：
2021-03-05
影响因子：
4.6
通讯作者：
Hyun CK
中科院分区：
文献类型：
--
作者：
Kwon J;Lee C;Heo S;Kim B;Hyun CK
考虑到炎症性肠病（IBD）患者中非酒精性脂肪性肝病（NAFLD）的高患病率，本研究旨在阐明肠道炎症性疾病与肝脂肪变性和血脂异常之间因果关系的分子机制。用急性或慢性葡聚糖硫酸钠（DSS）治疗的年轻和年老小鼠都发生了结肠炎，其表现为体重减轻、结肠长度缩短以及疾病活动指数和炎症评分升高。它们还显示肠屏障功能相关蛋白的表达降低和血浆脂多糖水平升高，表明DSS诱导的屏障功能障碍，从而增加了通透性。有趣的是，他们表现出肝脏脂肪堆积和血脂异常的表型。这种DSS诱导的结肠炎相关脂质代谢功能障碍是由于代谢过程的整体破坏，包括脂肪酸氧化、脂肪生成、脂解、胆固醇逆向转运、胆汁酸合成以及白色脂肪组织布朗宁和棕色脂肪组织产热，其中大部分由能量稳态的关键调节剂如FGF 21、脂联素和鸢尾素介导，通过SIRT 1/PGC-1α和LXRα依赖性途径。我们的研究表明了NAFLD和IBD合并症的潜在分子机制，这可能为了解这两种疾病的致病联系和发现治疗的关键治疗靶点提供关键。
Considering high prevalence of non-alcoholic fatty liver diseases (NAFLD) in patients with inflammatory bowel disease (IBD), this study aimed to elucidate molecular mechanisms for how intestinal inflammatory conditions are causally linked to hepatic steatosis and dyslipidemia. Both younger and older mice treated with acute or chronic dextran sodium sulfate (DSS) developed colitis, which was evidenced by weight loss, colon length shortening, and elevated disease activity index and inflammation score. They also showed decreased expression of intestinal barrier function-related proteins and elevated plasma lipopolysaccharide level, indicating DSS-induced barrier dysfunction and thereby increased permeability. Interestingly, they displayed phenotypes of hepatic fat accumulation and abnormal blood lipid profiles. This DSS-induced colitis-associated lipid metabolic dysfunction was due to overall disruption of metabolic processes including fatty acid oxidation, lipogenesis, lipolysis, reverse cholesterol transport, bile acid synthesis, and white adipose tissue browning and brown adipose tissue thermogenesis, most of which are mediated by key regulators of energy homeostasis such as FGF21, adiponectin, and irisin, via SIRT1/PGC-1α- and LXRα-dependent pathways. Our study suggests a potential molecular mechanism underlying the comorbidity of NAFLD and IBD, which could provide a key to understanding how the two diseases are pathogenically linked and discovering critical therapeutic targets for their treatment.
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影响因子：
4.3
作者：
Chao CY;Battat R;Al Khoury A;Restellini S;Sebastiani G;Bessissow T
通讯作者：
Bessissow T
影响因子：
12.8
作者：
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7.3
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影响因子：
5.6
作者：
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通讯作者：
Jain SK
影响因子：
4.6
作者：
Chelakkot C;Ghim J;Rajasekaran N;Choi JS;Kim JH;Jang MH;Shin YK;Suh PG;Ryu SH
通讯作者：
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