Metabolism reprogramming: new insights of Dlk1 into cardiac fibrosis

This commentary refers to ‘Deletion of delta-like 1 homologue accelerates fibroblast-myofibroblast differentiation and induces myocardial fibrosis’, by Rodriguez et al., 2019;40:967–978. We read with great interest the article by Rodriguez et al.1 deciphering novel anti-fibrogenic role of Dlk1 in the chronic cardiac fibrosis, which may provide new insights and therapeutic strategies for fibrotic disorders in the heart. The authors found that Dlk1-deficient mice exhibited the enhancement of cardiac fibrosis and myocyte hypertrophy and the impairment of heart function probably through down-regulation of miR-370 and then stimulation of TGF-β signalling and activation of myFB. However, Dlk1-null mice also displayed growth retardation and accelerated adiposity2 and targeting visceral adiposity recently was reported to be crucial to limit cardiac fibrosis via modulating the activation of fibroblasts,3 indicating that other bioactive factors, such as osteopontin or leptin might be involved in the cardiac fibrosis from mice lacking Dlk1 and highlighting the important interrelation between heart and other endocrine organs during adverse cardiac remodelling. Besides, previous study showed that increase with obesity was associated with the levels of soluble form of Dlk1 in serum and its levels significantly decreased in the patients with severe obesity after bariatric surgery.4 Marked weight loss in these patients was associated with amelioration of insulin resistance, reverse cardiac remodelling and improvement of heart function.5 At least, these clues seem to imply that excess Dlk1 in serum could be associated with the undesirable metabolism reprogramming, which might synergistically contribute to the progression of cardiac remodelling, and even increase susceptibility to other diseases such as anxiety, bone loss, and hepatocellular carcinoma progression. Conflict of interest: none declared.