Abstract
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.
Highlights
IntroductionSkeletal muscle is composed of multiple types of fibers that differ in terms of their morphological, biochemical, and physiological properties
Mammalian skeletal muscles consist of four types classified according to the type of myosin heavy chain expressed: type I, IIA, IIB, and IIX fibers can be distinguished by the predominant expression of MYH7, MYH2, MYH4, and MYH1, respectively[4,25,26]
One fundamental difference regards energy metabolism: male skeletal muscles preferentially utilize glycolysis, while female muscles tend to rely on mitochondrial fatty acid β-oxidation[7]
Summary
Skeletal muscle is composed of multiple types of fibers that differ in terms of their morphological, biochemical, and physiological properties In rodents, these fibers are largely divided into four types (types I, IIA, IIB, and IIX) based on which the myosin heavy chain (MYH) gene is expressed[2,3,4]. The preferred fuels for energy metabolism have been shown to be glucose and fatty acids in the muscles of males and females, respectively[12,13] This difference has been thought to play a fundamental role in the sexually dimorphic functions of skeletal muscle, the mechanisms that induce this feature remain unknown. Several genes whose functions are closely related to the male-biased anabolic activity of muscles were shown to be targets of AR22–24
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