Rebuttal to: Liver Steatosis is a Driving Factor of Inflammation.
Rebuttal to: Liver Steatosis is a Driving Factor of Inflammation.
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DOI：
10.1016/j.jcmgh.2022.01.005
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发表时间：
2022
影响因子：
7.2
通讯作者：
Raeman, R. E. B. E. N.
中科院分区：
文献类型：
--
作者：
Raeman, R. E. B. E. N.
脂肪肝是酒精性和非酒精性脂肪性肝病（NAFLD）的标志，其特征在于称为脂滴（LD）的脂质储存细胞器在肝细胞内积聚。LD的主要功能是维持细胞代谢，并通过在营养过剩期间储存过量的游离脂肪酸和胆固醇酯来保护细胞免受脂毒性。相反，LD在营养缺乏或组织生长期间充当能量来源。1在慢性或过量热量摄入期间，当脂质可用性超过LD螯合过量游离脂肪酸的能力时，LD在肝细胞中蓄积。然而，肝细胞内LD蓄积并不等同于细胞功能障碍，1并且支持肝细胞中LD过度蓄积与NAFLD进展之间存在联系的证据充其量是相关的。然而，过量的循环游离脂肪酸和脂质中间体在未能螯合到LD中的情况下，通过诱导脂毒性和免疫细胞的活化而导致肝脏炎症。2 Mooli及其同事在随附的观点对比文章中认为，脂毒性诱导的焦亡是NAFLD疾病进展的主要驱动因素。虽然脂肪肝确实促进了NAFLD的肝脏炎症，但认为过量脂质是NAFLD中脂肪肝最有影响力的促进剂可能是一个草率的假设。3NAFLD与肝细胞焦亡的一些最有效的诱导剂的增加的易位相关：肠道微生物产物。3，4研究表明，即使短期暴露于西方饮食也会增加健康受试者肠道微生物产物的易位，由此产生的内毒素血症不仅会刺激肝脏炎症，还会导致肝脂肪变性，这表明肠道
Hepatosteatosis, a hallmark of alcoholic and nonalcoholic fatty liver disease (NAFLD), is characterized by accumulation of lipid storage organelles called lipid droplets (LDs) within hepatocytes. LDs primarily function to maintain cellular metabolism and protect cells from lipotoxicity by storing excess free fatty acids and cholesterol esters during nutrient excess. Conversely, LDs serve as energy sources during periods of nutrient deprivation or tissue growth. 1 During chronic or excess caloric intake when lipid availability exceeds the capacity of LDs to sequester excess free fatty acids, LDs accumulate in hepatocytes. LD accumulation within hepatocytes, however, does not equate to cellular dysfunction, 1 and evidence supporting a link between excessive LD accumulation in hepatocytes and NAFLD progression is, at best, correlative. Excess circulating free fatty acids and lipid intermediates, in the event of failed sequestration into LDs, however, contribute to hepatic inflammation by inducing lipotoxicity and activation of immune cells. 2Mooli and coworkers in the accompanying point-counterpoint article argue that lipotoxicity-induced pyroptosis is the major driver of disease progression in NAFLD. Although pyroptosis does promote hepatic inflammation in NAFLD, it might be a hasty assumption to suggest that excess lipids are the most influential promoter of pyroptosis in NAFLD. 3 NAFLD is associated with increased translocation of some of the most potent inducers of hepatocyte pyroptosis: gut microbial products. 3, 4 Studies have shown that even short-term exposure to a western diet increases the translocation of gut microbial products in healthy subjects and the resulting endotoxemia not only galvanizes hepatic inflammation but also hepatosteatosis suggesting that gut
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DOI：
10.1016/j.jcmgh.2015.01.001
发表时间：
2015-03
影响因子：
7.2
作者：
Luther J;Garber JJ;Khalili H;Dave M;Bale SS;Jindal R;Motola DL;Luther S;Bohr S;Jeoung SW;Deshpande V;Singh G;Turner JR;Yarmush ML;Chung RT;Patel SJ
通讯作者：
Patel SJ
影响因子：
5
作者：
Kaden-Volynets, Valentina;Basic, Marijana;Bischoff, Stephan C.
通讯作者：
Bischoff, Stephan C.
影响因子：
29.4
作者：
Pendyala S;Walker JM;Holt PR
通讯作者：
Holt PR
影响因子：
29.4
作者：
Rahman K;Desai C;Iyer SS;Thorn NE;Kumar P;Liu Y;Smith T;Neish AS;Li H;Tan S;Wu P;Liu X;Yu Y;Farris AB;Nusrat A;Parkos CA;Anania FA
通讯作者：
Anania FA
影响因子：
29
作者：
Mauro C;Smith J;Cucchi D;Coe D;Fu H;Bonacina F;Baragetti A;Cermenati G;Caruso D;Mitro N;Catapano AL;Ammirati E;Longhi MP;Okkenhaug K;Norata GD;Marelli-Berg FM
通讯作者：
Marelli-Berg FM