Fibroblast growth factor 21 inhibition aggravates cardiac dysfunction in diabetic cardiomyopathy by improving lipid accumulation.
Fibroblast growth factor 21 inhibition aggravates cardiac dysfunction in diabetic cardiomyopathy by improving lipid accumulation.
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DOI：
10.3892/etm.2017.5375
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发表时间：
2018-01
影响因子：
2.7
通讯作者：
Shen E
中科院分区：
文献类型：
--
作者：
Chen C;Meng Z;Zheng Y;Hu B;Shen E
糖尿病性心肌病（DCM）是糖尿病患者发病和死亡的主要原因之一。最近的研究表明，DCM患者血浆中成纤维细胞生长因子21（FGF 21）水平升高，FGF 21已被证明是心脏的心血管保护剂。本研究旨在进一步探讨FGF 21在扩张型心肌病中的致病作用，推测FGF 21的缺失可能通过调节脂质代谢、心肌肥厚和心肌纤维化而促进扩张型心肌病的进展，从而加重心功能障碍。共44只小鼠随机分为正常组（n=6）、DCM组（n =6）、正常+ scrambled siRNA组（n =6）、DCM + scrambled siRNA组（n=6）、正常+FGF 21 siRNA组（n=10）和DCM + FGF 21 siRNA组（n=10）。DCM组小鼠注射链脲佐菌素诱导1型糖尿病模型，而FGF 21 siRNA抑制FGF 21表达。正常和给予乱序siRNA的DCM小鼠分别作为正常+FGF 21 siRNA和DCM + FGF 21 siRNA组的对照。在DCM组中，FGF 21抑制促进了心脏肥大和纤维化，其指标包括心房钠尿因子、α-骨骼肌动蛋白、I型和III型胶原以及转化生长因子-β的表达水平增加，导致心功能进一步下降。此外，DCM小鼠中的FGF 21抑制增加了脂滴的数量和心脏甘油三酯、血浆甘油三酯和胆固醇水平的浓度，伴随着过氧化物酶体增殖物激活受体γ共激活因子1α（PGC-1α）的下调和分化簇（CD）36的上调。因此，结果表明FGF 21抑制通过调节PGC-1α和CD 36的表达水平加重脂质积聚而加重心功能障碍。总之，提示FGF 21可能是治疗DCM的潜在有用的药剂。
Diabetic cardiomyopathy (DCM) is one of the major causes of morbidity and mortality in diabetic patients. Recent studies have demonstrated an increased level of fibroblast growth factor 21 (FGF21) in the plasma of DCM patients, and FGF21 has been proven to be a cardiovascular protector of the heart. The present study aimed to further investigate the pathogenic role of FGF21 in DCM, hypothesizing that a lack of FGF21 may promote the progression of DCM by regulating the lipid metabolism, cardiac hypertrophy and cardiac fibrosis, thus deteriorating the cardiac dysfunction. A total of 44 mice were randomly assigned into the normal (n=6), DCM (n=6), normal + scrambled siRNA (n=6), DCM + scrambled siRNA (n=6), normal + FGF21 siRNA (n=10) and DCM + FGF21 siRNA (n=10) groups. Type 1 diabetes mellitus was induced to mice in the DCM groups by streptozotocin injection, while FGF21 expression was inhibited by FGF21 siRNA. Normal and DCM mice administrated with scrambled siRNA were respectively regarded as the controls for the normal + FGF21 siRNA and DCM + FGF21 siRNA groups. In the DCM group, FGF21 inhibition promoted cardiac hypertrophy and fibrosis, and the expression levels of their indicators, including atrial natriuretic factor, α-skeletal actin, collagen type I and III, and transforming growth factor-β, increased, leading to further decreased cardiac function. In addition, FGF21 inhibition in DCM mice elevated the quantity of lipid droplets and the concentration of heart triglycerides, plasma triglycerides and cholesterol levels, accompanied by downregulation of peroxisome proliferator-activated receptor γ co-activator 1α (PGC-1α) and upregulation of cluster of differentiation (CD)36. Thus, the results indicated that FGF21 inhibition exacerbates the cardiac dysfunction by aggravating the lipid accumulation through regulating the expression levels of PGC-1α and CD36. In conclusion, it is suggested that FGF21 may be a potentially useful agent in the treatment of DCM.
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影响因子：
3.7
作者：
Lin Z;Wu Z;Yin X;Liu Y;Yan X;Lin S;Xiao J;Wang X;Feng W;Li X
通讯作者：
Li X
影响因子：
15.9
作者：
SILVERSTEIN, RL;ASCH, AS;NACHMAN, RL
通讯作者：
NACHMAN, RL
影响因子：
3.7
作者：
Muise ES;Souza S;Chi A;Tan Y;Zhao X;Liu F;Dallas-Yang Q;Wu M;Sarr T;Zhu L;Guo H;Li Z;Li W;Hu W;Jiang G;Paweletz CP;Hendrickson RC;Thompson JR;Mu J;Berger JP;Mehmet H
通讯作者：
Mehmet H
影响因子：
29
作者：
Badman, Michael K.;Pissios, Pavlos;Maratos-Flier, Eleftheria
通讯作者：
Maratos-Flier, Eleftheria
影响因子：
37.8
作者：
Koonen, Debby P. Y.;Febbraio, Maria;Dyck, Jason R. B.
通讯作者：
Dyck, Jason R. B.