Cardiac-to-adipose axis in metabolic homeostasis and diseases: special instructions from the heart

Figures

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  Fig. 1. Cardiokines-mediated communication in physiological and pathological conditions. Cardiokines can be divided into peptides, proteins, miRNAs and sEVs. The physiological regulation of adipose tissue includes lipolysis, adipogenesis, energy expenditure, browning of adipose tissue, and the synthesis and secretion of adipokines. While in pathological situations, cardiokine-mediated adipose regulation differs in several diseases. The cardiomyocyte-derived miR-23-27-24 impairs adipose tissue's metabolism and endocrine function by exacerbating adipose ER stress in AMI. In CHD models, the cardiomyocyte-derived BNP leads to metabolic disorder and abnormal adiponectin secretion in adipose tissue. At the same time, adipokines in obesity and diabetes play a vital role in insulin resistance, systemic metabolism, lipid metabolism in AT, adipocyte cell size, adipogenesis, adipose tissue browning, the anti-contractile effect, adipose inflammation and angiogenesis in BAT

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  Fig. 2. Underlying upstream and downstream mechanisms of cardiokines that mediate the heart-to-adipose tissue communication. Under physiological conditions, cardiomyocytes are the primary source of cardiokines, including the cardiomyocyte-derived ANP and BNP. Autophagy and cardiac corin regulators ANP synthesis and secretion in cardiomyocytes. When exposed to cold temperatures, ANP down-regulates LDL metabolism by decreasing adipocyte LDLR through the PCSK1 pathway. Meanwhile, cardiomyocyte-derived BNP increases mTORC1 expression and promotes the phosphorylation of S6K1 and S6 through the PKG/p-PKG signaling pathway. While in pathological conditions, cardiokines are derived from cardiomyocytes, cardiac fibroblasts and endothelial cells. EC-mediated miR-409-3p inhibits PLGF expression and angiogenesis in BAT through ZEB1 and MAP4K3 activation. Fibroblast-mediated miR-21-3p suppresses the FGFR1 in adipocytes and impairs the combination of FGF21-FGFR1 through direct binding with FGFR1 mRNA. In addition, the cardiomyocyte-derived FSTL1 inhibits the phosphorylation of PPARγ through the integrin β1-FAK/ERK signaling by the N-glycosylation of FSTL1 in the N142 site. Cardiomyocyte-derived…