FGF21 in obesity and cancer: New insights.
FGF21 in obesity and cancer: New insights.
复制标题
肥胖和癌症中的FGF21：新见解。
DOI：
10.1016/j.canlet.2020.11.026
复制
发表时间：
2021-02-28
期刊：
影响因子：
9.7
通讯作者：
Luo Y
中科院分区：
文献类型：
--
作者：
Lu W;Li X;Luo Y
内分泌FGF21是2005年被发现的一种新的代谢调节剂，其新的功能来源于经典的肝素结合的FGFs，它不依赖于辅受体直接促进细胞的增殖和生长。早期的研究表明，FGF21是肝脏以及其他几个内分泌和代谢组织中的应激感受器。肝脏FGF21信号通过内分泌途径抑制代谢紊乱，促进代谢动态平衡。小鼠和人类研究的趋同表明，FGF21促进脂质分解代谢，包括脂肪分解、脂肪酸氧化、线粒体氧化活性和生热能量消耗，而不是直接调节胰岛素和食欲。白色和棕色的脂肪组织，以及某种程度上的下丘脑，都是肝脏或药理上FGF21的重要组织和分子靶点，它们都是FGFR1和辅助受体KLb的跨膜受体二元复合体。另一方面，越来越多的研究表明，胰腺腺泡细胞形成了FGF21的组成性高产部位，然后FGF21以自分泌或旁分泌模式发挥作用。除了对大量营养素代谢和生理能量消耗的调节外，FGF21似乎还可以预防脂肪胰腺、脂肪性胰腺炎、脂肪肝和脂肪性肝炎的发展，从而防止胰腺导管腺癌或肝细胞癌等晚期病理的发展。这篇综述旨在提供这些新发现的最新进展，阐明FGF21-FGFR1-KLB信号通路在代谢异常相关的严重组织损伤和恶性肿瘤中的保护作用，并通过降低代谢风险和炎症，为肥胖引起的癌症患者提供潜在的预防或治疗策略。
The endocrine FGF21 was discovered as a novel metabolic regulator in 2005 with new functions bifurcating from the canonic heparin-binding FGFs that directly promote cell proliferation and growth independent of a co-receptor. Early studies have demonstrated that FGF21 is a stress sensor in the liver and possibly, several other endocrine and metabolic tissues. Hepatic FGF21 signals via endocrine routes to quench episodes of metabolic derangements, promoting metabolic homeostasis. The convergence of mouse and human studies shows that FGF21 promotes lipid catabolism, including lipolysis, fatty acid oxidation, mitochondrial oxidative activity, and thermogenic energy dissipation, rather than directly regulating insulin and appetite. The white and brown adipose tissues and, to some extent, the hypothalamus, all of which host a transmembrane receptor binary complex of FGFR1 and co-receptor KLB, are considered the essential tissue and molecular targets of hepatic or pharmacological FGF21. On the other hand, a growing body of work has revealed that pancreatic acinar cells form a constitutive high-production site for FGF21, which then acts in an autocrine or paracrine mode. Beyond regulation of macronutrient metabolism and physiological energy expenditure, FGF21 appears to function in forestalling the development of fatty pancreas, steato-pancreatitis, fatty liver, and steatohepatitis, thereby preventing the development of advanced pathologies such as pancreatic ductal adenocarcinoma or hepatocellular carcinoma. This review is intended to provide updates on these new discoveries that illuminate the protective roles of FGF21-FGFR1-KLB signal pathway in metabolic anomalies-associated severe tissue damage and malignancy, and to inform potential new preventive or therapeutic strategies for obesity-inflicted cancer patients via reducing metabolic risks and inflammation.
登录
查看更多内容
影响因子：
29
作者：
Coate KC;Hernandez G;Thorne CA;Sun S;Le TDV;Vale K;Kliewer SA;Mangelsdorf DJ
通讯作者：
Mangelsdorf DJ
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
2.9
作者：
Abbruzzese JL;Andersen DK;Borrebaeck CAK;Chari ST;Costello E;Cruz-Monserrate Z;Eibl G;Engleman EG;Fisher WE;Habtezion A;Kim SK;Korc M;Logsdon C;Lyssiotis CA;Pandol SJ;Rustgi A;Wolfe BM;Zheng L;Powers AC
通讯作者：
Powers AC
影响因子：
5
作者：
Andersen, Birgitte;Omar, Bilal A.;Ahren, Bo
通讯作者：
Ahren, Bo
影响因子：
16.6
作者：
Han HS;Choi BH;Kim JS;Kang G;Koo SH
通讯作者：
Koo SH