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 miR-208a decreases MED13 expression by inhibiting MED13 mRNA translation through miR-208a-MED13 mRNA combination