Deficiency of Cathelicidin Attenuates High-Fat Diet Plus Alcohol-Induced Liver Injury through FGF21/Adiponectin Regulation.
Deficiency of Cathelicidin Attenuates High-Fat Diet Plus Alcohol-Induced Liver Injury through FGF21/Adiponectin Regulation.
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作者：
Li F;Chen J;Liu Y;Gu Z;Jiang M;Zhang L;Chen SY;Deng Z;McClain CJ;Feng W
饮酒和肥胖是脂肪性肝炎的已知危险因素。在这里，我们报告说，CRAMP（cathelicidin-related antimicrobial peptide-gene name：Camp）的缺陷是对高脂饮食（HFD）加急性酒精（HFDE）诱导的肝损伤的保护。HFDE在WT小鼠中显著诱导肝损伤和脂肪变性，而在Camp-/-小鼠中减弱。Camp-/-小鼠肝脏中的神经元浸润减少。喂食HFDE显著增加WT小鼠的附睾白色脂肪组织（eWAT）质量并诱导脂肪细胞肥大，而这些作用通过删除Camp而减弱。此外，Camp-/-小鼠具有显著增加的eWAT脂解，通过脂解酶、脂肪甘油三酯脂肪酶（ATGL）和脂肪敏感性脂肪酶（HSL）的上调表达来证明。cAMP的消耗也增加了小鼠棕色脂肪组织（BAT）中解偶联蛋白1（UCP 1）依赖的产热作用。HFDE喂养的Camp-/-小鼠在eWAT中具有升高的成纤维细胞生长因子21（FGF 21）蛋白水平，具有增加的脂联素产生，其已被证明减轻肝脏脂肪沉积和炎症。总的来说，我们已经证明，通过FGF 21/脂联素调节，Camp-/-小鼠可免受HFD加酒精诱导的肝损伤和脂肪变性。靶向CRAMP可能是预防/治疗高脂饮食加饮酒诱导的脂肪性肝炎的有效方法。
Alcohol consumption and obesity are known risk factors of steatohepatitis. Here, we report that the deficiency of CRAMP (cathelicidin-related antimicrobial peptide—gene name: Camp) is protective against a high-fat diet (HFD) plus acute alcohol (HFDE)-induced liver injury. HFDE markedly induced liver injury and steatosis in WT mice, which were attenuated in Camp–/– mice. Neutrophil infiltration was lessened in the liver of Camp–/– mice. HFDE feeding dramatically increased epididymal white adipose tissue (eWAT) mass and induced adipocyte hypertrophy in WT mice, whereas these effects were attenuated by the deletion of Camp. Furthermore, Camp–/– mice had significantly increased eWAT lipolysis, evidenced by up-regulated expression of lipolytic enzymes, adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL). The depletion of Camp also increased uncoupling protein 1 (UCP1)-dependent thermogenesis in the brown adipose tissue (BAT) of mice. HFDE fed Camp–/– mice had elevated protein levels of fibroblast growth factor 21 (FGF21) in the eWAT, with an increased adiponectin production, which had been shown to alleviate hepatic fat deposition and inflammation. Collectively, we have demonstrated that Camp–/– mice are protected against HFD plus alcohol-induced liver injury and steatosis through FGF21/adiponectin regulation. Targeting CRAMP could be an effective approach for prevention/treatment of high-fat diet plus alcohol consumption-induced steatohepatitis.
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