Fig 2: rMyonectin protects cardiac mitochondria in LPS-induced sepsis-induced cardiomyopathy mice by promoting mitochondrial biogenesis and maintaining mitochondrial dynamics. (A) The ATP content in myocardial tissue. (B) Mitochondrial ultrastructure of myocardial tissue was observed by TEM. Magnification, ×3,000, ×7,000 and ×20,000. (C) Western blot analysis and semi-quantification of PGC-1α, NRF1, TFAM, OPA1, Mfn2, p-Drp1 at Ser616 and Drp1 in myocardial tissue. The data are presented as mean±SEM. **P<0.01, ***P<0.001, ****P<0.0001. rMyonectin, recombinant myonectin; TEM, transmission electron microscopy; PGC-1α, peroxisome proliferator-activated receptor γ co-activator-1 α; NRF1, nuclear respiratory factor 1; TFAM, mitochondrial transcription factor A; Mfn2, mitofusin 2; OPA1, optic atrophy 1; Drp1, dynamin-related protein 1; LPS, lipopolysaccharide; p-, phosphorylated.

Fig 3: AdipoR1 knockdown abolishes the protective effect of rMyonectin against LPS-induced mitochondrial dysfunction in cardiomyocytes. (A) The ATP content in NMCMs. (B) Relative OCR. (C) Detection of the activities of mitochondrial respiratory chain complexes I and III. (D) Analysis of MMP using JC-1 staining. Scale bar, 50 μm. (E) Western blot analysis and semi-quantification of PGC-1α, NRF1, TFAM, OPA1, Mfn2, p-Drp1 at Ser616 and Drp1 in NMCMs. The data are presented as mean±SEM. *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001. rMyonectin, recombinant myonectin; NMCMs, neonatal mouse cardiomyocytes; AdipoR1, adiponectin receptor 1; AMPK, AMP-activated protein kinase; OCR, oxygen consumption rate; MMP, mitochondrial membrane potential; PGC-1α, peroxisome proliferator-activated receptor γ co-activator-1 α; NRF1, nuclear respiratory factor 1; TFAM, mitochondrial transcription factor A; Mfn2, mitofusin 2; OPA1, optic atrophy 1; Drp1, dynamin-related protein 1; si, small interfering RNA; NC, negative control; siAdipoR1, siRNA targeting AdipoR1; LPS, lipopolysaccharide; p-, phosphorylated.

Fig 4: Molecular mechanism by which rMyonectin ameliorates SIC. rMyonectin ameliorates SIC by alleviating mitochondrial dysfunction and inhibiting cardiomyocyte apoptosis via activation of the AdipoR1/AMPK pathway. rMyonectin, recombinant myonectin; SIC, sepsis-induced cardiomyopathy; OMM, outer mitochondrial membranes; IMM, inner mitochondrial membranes; AdipoR1, adiponectin receptor 1; AMPK, AMP-activated protein kinase; PGC-1α, peroxisome proliferator-activated receptor γ co-activator-1 α; NRF1, nuclear respiratory factor 1; TFAM, mitochondrial transcription factor A; Mfn2, mitofusin 2; OPA1, optic atrophy 1; Drp1, dynamin-related protein 1; I, mitochondrial respiratory chain complex I; III, mitochondrial respiratory chain complex III; p-, phosphorylated.

Fig 5: rMyonectin protects cardiac mitochondria in CLP-induced sepsis-induced cardiomyopathy mice by promoting mitochondrial biogenesis and maintaining mitochondrial dynamics. (A) The ATP content in myocardial tissue. (B) Mitochondrial ultrastructure of myocardial tissue was observed by TEM. Magnification, ×3,000, ×7,000 and ×20,000. (C) Western blot analysis and semi-quantification of PGC-1α, NRF1, TFAM, OPA1, Mfn2, p-Drp1 at Ser616 and Drp1 in myocardial tissue. The data are presented as mean±SEM. *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001. rMyonectin, recombinant myonectin; CLP, cecal ligation and puncture; TEM, transmission electron microscopy; PGC-1α, peroxisome proliferator-activated receptor γ co-activator-1 α; NRF1, nuclear respiratory factor 1; TFAM, mitochondrial transcription factor A; Mfn2, mitofusin 2; OPA1, optic atrophy 1; Drp1, dynamin-related protein 1; p-, phosphorylated.