Sex differences in metabolic pathways are regulated by Pfkfb3 and Pdk4 expression in rodent muscle.
Antonius ChristiantoTakashi BabaFumiya TakahashiKai InuiMiki InoueMikita SuyamaYusuke OnoYasuyuki OhkawaKen-Ichirou MorohashiPublished in: Communications biology (2021)
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.
Keyphrases
- poor prognosis
- fatty acid
- skeletal muscle
- genome wide
- single cell
- type diabetes
- polycystic ovary syndrome
- genome wide identification
- endothelial cells
- bioinformatics analysis
- pregnant women
- adipose tissue
- dna methylation
- gene expression
- tyrosine kinase
- insulin resistance
- protein kinase
- transcription factor
- genome wide analysis
- estrogen receptor