Fig. 4: Akkermansia muciniphila (A. muciniphila) administration regulates mitochondrial bioenergetics by activating PPARα/PGC1α signaling pathway.

a Pearson correlation analysis between the 11 mitochondrial OXPHOS-related genes and A. muciniphila levels, as well as cardiac injury markers in mice (n = 3). b, c Representative immunoblotting images and quantification of PPARα and PGC1α in the heart tissues from the control, DOX, and DOX + A. muciniphila groups (n = 3). d RT-qPCR was used to measure the mRNA levels of PPARA and PGC1α, from the heart tissues in the indicated groups (n = 3). e Immunofluorescence staining of heart tissues from the indicated groups with cardiac PPARα (green) DAPI (blue), as well as semi-quantitative analysis of PPAR fluorescence. f Schematic representation of treatment with DOX, A. muciniphila, or PPARα inhibitor NXT629 (30 mg/kg). g Anatomic M-mode echocardiography and corresponding electrocardiographic images of hearts from DOX, DOX + A. muciniphila, and DOX + A. muciniphila + NXT629 (n = 6). Changes of echocardiographic h left ventricular ejection fraction (LVEF) and i left ventricular fraction shortening (LVFS) in the indicated groups (n = 6). j Representative images of myocardial tissue sections stained with Masson’s trichrome (from top to bottom, a transverse section and a longitudinal section). Quantification of the fractional area of cardiac fibrosis based on 6 randomly selected fields of stained myocardial tissue sections (n = 6). k Representative transmission electron microscopy images of mice hearts from the three group. Scale bar = 2 μm. % mitochondrial area refers to the ratio of mitochondrial area to image area (n = 6). Data presented as mean ± SD. For statistical analysis, two-way ANOVA with Tukey’s test for multiple comparisons was used. *P < 0.05, **P < 0.01, ***P < 0.001.