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

Publisher: Nature Publishing Group UK Country of Publication: England NLM ID: 101719179 Publication Model: Electronic Cited Medium: Internet ISSN: 2399-3642 (Electronic) Linking ISSN: 23993642 NLM ISO Abbreviation: Commun Biol Subsets: MEDLINE

Original Publication: London, United Kingdom : Nature Publishing Group UK, [2018]-

Muscle Fibers, Fast-Twitch/*metabolism ; Phosphofructokinase-2/*genetics ; Pyruvate Dehydrogenase Acetyl-Transferring Kinase/*genetics; Animals ; Female ; Male ; Metabolic Networks and Pathways ; Mice ; Mice, Inbred C57BL ; Phosphofructokinase-2/metabolism ; Pyruvate Dehydrogenase Acetyl-Transferring Kinase/metabolism ; Sex Factors

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.
(© 2021. The Author(s).)

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0 (Pdk4 protein, mouse)
0 (Pyruvate Dehydrogenase Acetyl-Transferring Kinase)
EC 2.7.1.105 (PFKFB3 protein, mouse)
EC 2.7.1.105 (Phosphofructokinase-2)

Date Created: 20211105 Date Completed: 20211217 Latest Revision: 20211217

20250114

PMC8569015

10.1038/s42003-021-02790-y

34737380