Fig. 8

Proposed model for the protective effects of adiponectin on dystrophic muscle. Signal transduction mediating ApN protection on dystrophic muscle: binding of ApN to AdipoR1 activates the AMPK/SIRT1/PGC-1α pathway. Briefly, ApN leads to AMPK phosphorylation/activation. P-AMPK in turn phosphorylates PGC-1α and indirectly increases the expression of SIRT1 (through rising NAD+/NADH ratio). SIRT1 in turn deacetylates and fully activates PGC-1α. Next, PGC-1α represses NF-κB activity by dephosphorylation of the p65 subunit [38], while SIRT1 represses it by deacetylation [39]. This results in decreased muscle inflammation/oxidative stress and improved myogenic program as well as enhanced utrophin expression and oxidative capacity, both processes helping rescue the dystrophic phenotype. Green arrow, stimulation; red arrow, inhibition