Elevated whole muscle phosphatidylcholine: phosphatidylethanolamine ratio coincides with reduced SERCA activity in murine overloaded plantaris muscles.

BACKGROUND

An increase in phosphatidylcholine:phosphatidylethanolamine (PC:PE) and a decrease in fatty acyl chain length, monounsaturated:polyunsaturated (MUFA:PUFA) fatty acyl ratio reduces SERCA activity in liposomes and in mouse models of obesity and muscular dystrophy. We have previously shown that maximal SERCA activity is significantly reduced in mechanically overloaded (OVL) plantaris, however, whether changes in PC:PE ratio or fatty acyl composition may contribute to the alterations in maximal SERCA activity remain unknown. Here, we tested the hypotheses that in OVL plantaris 1) PC:PE ratio would negatively correlate with maximal SERCA activity and 2) PC fatty acyl chain length (ACL) and/or MUFA:PUFA ratio would positively correlate with maximal SERCA activity.

METHODS

To overload plantaris in mice, we transected the soleus and gastrocnemius tendons from one leg, while the contralateral leg underwent a sham surgery. After two weeks, plantaris muscles were extracted, homogenized and processed for SERCA activity and lipid analyses. Specifically, we performed HPTLC densitometry to examine changes in PC, PE, and the ratio of PC:PE. We also performed gas chromatography to assess any potential changes to fatty acyl composition.

RESULTS

SERCA activity was significantly reduced in OVL plantaris compared with sham. Coinciding with this, we found a significant increase in PC but not PE in OVL plantaris. In turn, there was an increase in PC:PE but did not reach significance (p = 0.09). However, we found a significant negative correlation between PC:PE and maximal SERCA activity. Fatty acyl composition of PE remained similar between OLV and sham and PC demonstrated higher percent mole fraction of 17:1, 18:1, and ACL compared to sham. In addition, PC ACL, % MUFA, % PUFA, or MUFA:PUFA did not significantly correlate with maximal SERCA activity.

CONCLUSIONS

Our results indicate that the phospholipid headgroup PC:PE negatively correlated and could potentially contribute to reductions in SERCA activity seen in functionally overloaded plantaris. In contrast, fatty acyl chain (ACL, % MUFA, % PUFA, MUFA:PUFA) did not correlate with maximal SERCA activity. Future studies will determine whether altering PC:PE with genetic and dietary interventions can influence SERCA activity and ultimately change the physiological outcome in response to muscle overloading.