Omentin-1 attenuates glucocorticoid-induced cardiac injury by phosphorylating GSK3β

Glucocorticoid excess often causes a variety of cardiovascular complications, including hypertension, atherosclerosis, and cardiac hypertrophy. To abrogate its cardiac side effects, it is necessary to fully disclose the pathophysiological role of glucocorticoid in cardiac remodelling. Previous clini...

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Veröffentlicht in:Journal of molecular endocrinology Jg. 66; H. 4; S. 273
Hauptverfasser: Jin, Zhousheng, Xia, Fangfang, Dong, Jiaojiao, Lin, Tingting, Cai, Yaoyao, Chen, Jiali, Chen, Xixi, Huang, Zhenyang, Wang, Quanguang, Chen, Hongfei, Zhang, Junkai
Format: Journal Article
Sprache:Englisch
Veröffentlicht: England 01.05.2021
Schlagworte:
Animals
Cardiomegaly - chemically induced
Cardiomegaly - genetics
Cardiomegaly - therapy
Cushing Syndrome - blood
Cushing Syndrome - genetics
Cushing Syndrome - pathology
Cytokines - genetics
Female
Glucocorticoids - blood
Glucocorticoids - toxicity
Glycogen Synthase Kinase 3 beta - genetics
Healthy Volunteers
Humans
Lectins - genetics
Male
Mitochondria - genetics
Phosphorylation - genetics
Rats
Signal Transduction - genetics
glucocorticoid excess
cardiac remodelling
glycogen synthase kinase 3β
omentin-1
mitochondria
ISSN:1479-6813, 1479-6813
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Zusammenfassung:Glucocorticoid excess often causes a variety of cardiovascular complications, including hypertension, atherosclerosis, and cardiac hypertrophy. To abrogate its cardiac side effects, it is necessary to fully disclose the pathophysiological role of glucocorticoid in cardiac remodelling. Previous clinical and experimental studies have found that omentin-1, one of the adipokines, has beneficial effects in cardiovascular diseases, and is closely associated with metabolic disorders. However, there is no evidence to address the potential role of omentin-1 in glucocorticoid excess-induced cardiac injuries. To uncover the links, the present study utilized rat model with glucocorticoid-induced cardiac injuries and clinical patients with abnormal cardiac function. Chronic administration of glucocorticoid excess reduced rat serum omentin-1 concentration, which closely correlated with cardiac functional parameters. Intravenous administration of adeno-associated virus encoding omentin-1 upregulated the circulating omentin-1 level and attenuated glucocorticoid excess-induced cardiac hypertrophy and functional disorders. Overexpression of omentin-1 also improved cardiac mitochondrial function, including the reduction of lipid deposits, induction of mitochondrial biogenesis, and enhanced mitochondrial activities. Mechanistically, omentin-1 phosphorylated and activated the GSK3β pathway in the heart. From a study of 28 patients with Cushing's syndrome and 23 healthy subjects, the plasma level of glucocorticoid was negatively correlated with omentin-1, and was positively associated with cardiac ejection fraction and fractional shortening. Collectively, the present study provided a novel role of omentin-1 in glucocorticoid excess-induced cardiac injuries and found that the omentin-1/GSK3β pathway was a potential therapeutic target in combating the side effects of glucocorticoid.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1479-6813
1479-6813
DOI:10.1530/JME-20-0236