Am J Physiol Endocrinol Metab.: co-auth.: W.Wahli

Am J Physiol Endocrinol Metab. 2015 Apr 28:ajpendo.00586.2014. doi: 10.1152/ajpendo.00586.2014.

Inactivation of PPAR β/δ adversely affects satellite cells and reduces postnatal myogenesis.


PPAR β/δ is a ubiquitously expressed gene with higher levels observed in skeletal muscle. Recently, we showed that PPAR β/δ modulates Myostatin activity to induce myogenesis in skeletal muscle. In the present study, we show that PPAR β/δ-null mice display reduced body weight, skeletal muscle weight and myofibre atrophy during postnatal development. In addition, a significant reduction in satellite cell number was observed in PPAR β/δ-null mice, suggesting a role for PPAR β/δ in muscle regeneration. In order to investigate this, Tibialis Anterior muscles were injured with notexin and muscle regeneration was monitored on days 3, 5, 7 and 28-post injury. Immunohistochemical analysis revealed an increased inflammatory response and reduced myoblast proliferation in regenerating muscle from PPAR β/δ-null mice. Histological analysis confirmed that the regenerated muscle fibers of PPAR β/δ-null mice maintained an atrophy phenotype with reduced numbers of centrally placed nuclei. Even though satellite cell numbers were reduced prior to injury, satellite cell self-renewal was found to be unaffected in PPAR β/δ-null mice after regeneration. Previously we had showed that inactivation of PPAR β/δ increases myostatin signaling and inhibits myogenesis. Our results here confirm that inactivation of myostatin signaling rescues the atrophy phenotype and improves muscle fiber cross-sectional area in both uninjured and regenerated TA muscle from PPAR β/δ-null mice. Taken together, these data suggest that absence of PPAR β/δ leads to loss of satellite cells, impaired skeletal muscle regeneration and postnatal myogenesis. Furthermore, our results also demonstrate that functional antagonism of myostatin has utility in rescuing these effects.

Copyright © 2015, American Journal of Physiology – Endocrinology and Metabolism.


PPAR β/δ; myostatin; skeletal muscle regeneration

PMID: 25921579