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

• Published in: Communications biology 2021-11, Vol.4 (1), p.1264-1264, Article 1264
• Main Authors: Christianto, Antonius, Baba, Takashi, Takahashi, Fumiya, Inui, Kai, Inoue, Miki, Suyama, Mikita, Ono, Yusuke, Ohkawa, Yasuyuki, Morohashi, Ken-ichirou
• Format: Article
• Language: English
• Subjects: 13; 13/51; 14; 14/19; 14/34; 17β-Estradiol; 38; 38/39; 38/77; 38/89; 38/90; 631/45/320; 631/45/776/812; 64; 64/60; 82; Animals; Biology; Biomedical and Life Sciences; Energy metabolism; Estrus cycle; Female; Gender differences; Glycolysis; Life Sciences; Male; Males; Metabolic Networks and Pathways; Metabolic pathways; Metabolism; Mice; Mice, Inbred C57BL; Muscle Fibers, Fast-Twitch - metabolism; Oxidation; Phosphofructokinase; Phosphofructokinase-2 - genetics; Phosphofructokinase-2 - metabolism; Pyruvate Dehydrogenase Acetyl-Transferring Kinase - genetics; Pyruvate Dehydrogenase Acetyl-Transferring Kinase - metabolism; Pyruvic acid; Quadriceps muscle; Sex differences; Sex Factors; Sexes; Sexual dimorphism; Skeletal muscle; Steroids; Transcriptomes
• ISSN: 2399-3642; 2399-3642
• DOI: 10.1038/s42003-021-02790-y

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. Baba et al. analyzed the transcriptomes from quadriceps type IIB fibers of untreated, gonadectomized, and sex steroid-treated mice of both sexes and identified Pfkfb3 and Pdk4 as differentially regulated genes between males and diestrus females. The authors found that Pfkfb3 and Pdk4 may act as metabolic switches, showed male-enriched and estradiol-enhanced expression, respectively and contributed to sexually dimorphic metabolism.