Papers of the Week

Glucocorticoid excess often causes 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 omentin-1, one of adipokines, exists beneficial effects in cardiovascular diseases, and 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 suppressed the rat serum omentin-1 concentration, which closely correlated with cardiac functional parameters. Intravenous administration of adeno-associated virus encoding omentin-1 upregulated circulating omentin-1 level, and attenuated glucocorticoid excess-induced cardiac hypertrophy, and functional disorders. Overexpression of omentin-1 also improved cardiac mitochondrial function, including reduction of lipid deposits, induction of mitochondrial biogenesis, and enhanced mitochondrial activities. Mechanistically, omentin-1 phosphorylated and activated GSK3β pathway in hearts. From a study of 28 patients with Cushing's syndrome and 23 healthy subjects, plasma level of glucocorticoid was negatively correlated with omentin-1, which exhibiting positively association 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 omentin-1/GSK3β pathway was a potential therapeutic target in combating side effects of glucocorticoid.