Role of adiponectin in the metabolism of skeletal muscles in collagen VI–related myopathies


The role of adiponectin has been particularly deepened in diabetic muscles while the study of adiponectin in hereditary myopathies has been marginally investigated. Here, we report the study about adiponectin effects in Col6a1−/− (collagen VI–null) mice. Col6a1−/− mice show myophatic phenotype closer to that of patients with Bethlem myopathy, thus representing an excellent animal model for the study of this hereditary disease. Our findings demonstrate that Col6a1−/− mice have decreased plasma adiponectin content and diseased myoblasts have an impaired autocrine secretion of the hormone. Moreover, Col6a1−/− myoblasts show decreased glucose uptake and mitochondria with depolarized membrane potential and impaired functionality, as supported by decreased oxygen consumption. Exogenous addition of globular adiponectin modifies the features of Col6a1−/− myoblasts, becoming closer to that of the healthy myoblasts. Indeed, globular adiponectin enhances glucose uptake in Col6a1−/− myoblasts, modifies mitochondrial membrane potential, and restores oxygen consumption, turning closer to those of wild-type myoblasts. Finally, increase of plasma adiponectin level in Col6a1−/− mice is induced by fasting, a condition that has been previously shown to lead to the amelioration of the dystrophic phenotype. Collectively, our results demonstrate that exogenous replenishment of adiponectin reverses metabolic abnormalities observed in Col6a1−/− myoblasts.

Key messages

  • Col6a1−/− mice have decreased level of plasma adiponectin.

  • Myoblasts from Col6a1−/− muscles have impaired local adiponectin secretion.

  • Col6a1−/− myoblasts reveal altered metabolic features.

  • Addition of exogenous adiponectin ameliorates Col6a1−/− metabolic features.

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This work was supported by the Italian Ministry of University and Research (MIUR).

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Corresponding author

Correspondence to Tania Fiaschi.

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Mouse procedures were approved by the Ethics Committee of the University of Padua and authorized by the Italian Ministry of Health according to D. Lgs. 26/2014 implementing Directive 2010/63/EU.

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Supplementary figure 1

Analysis of adiponectin in females ofCol6a1–/–mice. A) Plasma adiponectin level obtained using ELISA test and reported as percentage of decrease of Col6a1–/– in comparison to WT. n=5 mice/group. *p<0.01; acrp30: adiponectin. B) Intracellular level of adiponectin in diaphragm and tibialis anterior by immunoblot. GAPDH immunoblot has been used for normalization. Bar graphs show the expression level of adiponectin reported as arbitrary unit (a.u.). (PNG 56 kb)

Supplementary figure 2.

Confocal images of myoblasts isolated from diaphragm of WT and Col6a1–/– mice incubated with (right panel), or without (left panel) gAd (1 μg/ml) for 30 minutes. The intracellular location of GLUT4 is shown as green signal obtained using a specific primary anti-GLUT4 antibody (ThermoFisher Scientific) and a secondary antibody conjugated to Alexa-488. Nuclei have been labelled with DAPI. The images are representative of three independent experiments. gAd: globular adiponectin. (PNG 242 kb)


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Gamberi, T., Magherini, F., Mannelli, M. et al. Role of adiponectin in the metabolism of skeletal muscles in collagen VI–related myopathies. J Mol Med 97, 793–801 (2019).

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  • Plasma adiponectin
  • Myophatic phenotype
  • Metabolism