Sex differences in metabolic pathways are regulated by Pfkfb3 and Pdk4 expression in rodent muscle

Antonius Christianto, Takashi Baba, Fumiya Takahashi, Kai Inui, Miki Inoue, Mikita Suyama, Yusuke Ono, Yasuyuki Ohkawa, Ken ichirou Morohashi

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)


Skeletal muscles display sexually dimorphic features. Biochemically, glycolysis and fatty acid β-oxidation occur preferentially in the muscles of males and females, respectively. However, the mechanisms of the selective utilization of these fuels remains elusive. Here, we obtain transcriptomes from quadriceps type IIB fibers of untreated, gonadectomized, and sex steroid-treated mice of both sexes. Analyses of the transcriptomes unveil two genes, Pfkfb3 (phosphofructokinase-2) and Pdk4 (pyruvate dehydrogenase kinase 4), that may function as switches between the two sexually dimorphic metabolic pathways. Interestingly, Pfkfb3 and Pdk4 show male-enriched and estradiol-enhanced expression, respectively. Moreover, the contribution of these genes to sexually dimorphic metabolism is demonstrated by knockdown studies with cultured type IIB muscle fibers. Considering that skeletal muscles as a whole are the largest energy-consuming organs, our results provide insights into energy metabolism in the two sexes, during the estrus cycle in women, and under pathological conditions involving skeletal muscles.

Original languageEnglish
Article number1264
JournalCommunications Biology
Issue number1
Publication statusPublished - Dec 2021

All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)


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