Sexual-Dimorphism in Exercise-Induced Beiging and Altered Mitochondrial Function in Inguinal White Adipose Tissue (iWAT) from the Mouse

Abstract

Regular physical exercise has numerous benefits on metabolic health, likely involving adaptations to many tissues, including adipose tissue. There are conflicting reports on the effects of exercise training on adaptations to iWAT and we hypothesized that these discrepancies may stem in part from sex-specific differences. Male and female 10 week old C57BL6/J mice were housed in cages with (trained) or without (sedentary) running wheels for 11 days (n=6-9/sex/experiment). Males performed less voluntary exercise vs. females (56±7 vs. 78±5 km; p<0.05). In males, training decreased iWAT fat pad weight (19.6%) and adipocyte size (19%) (both p<0.05), whereas training did not have these effects on iWAT in females, most likely due to increased food intake. Training did not alter perigonadal WAT weight or adipocyte size in either sex. In iWAT, training in males increased mRNA of the beiging genes Ucp1 (304%; p<0.01); Pgc1α (228%; p<0.05); Cidea (206%; p<0.05); and Dio2 (197%; p<0.01), as well as Ucp1 protein (124%; p<0.01), but none of these markers were increased in females. Exercise training also increased mitochondrial parameters in iWAT only from males, including basal respiration (170%; p<0.01), glycolytic capacity (227%; p<0.001) and the mitochondrial fission genes Opa1 (235%; p<0.05), Mfn1 (231%; p<0.001), and Mfn2 (229%; p<0.01). Since exercise may increase testosterone in male mice, we tested the effects of testosterone on iWAT beiging and mitochondria. iWAT of male and female mice were treated with testosterone (10μM) for 24 hours. Interestingly, testosterone increased Ucp1 protein (175%; p<0.05) and mRNA (386%; p<0.05) in iWAT from male, but not in females. We conclude that voluntary wheel running in mice results in beiging and mitochondrial adaptations to iWAT exclusively in males. Sex-specific differences in WAT function will be important to consider in all research investigating adipose tissue beiging and mitochondrial function. Disclosure P. Nigro: None. R. Middelbeek: None. C.R. Alves: None. B.G. Albertson: None. L.A. Rowland: None. A.B. Wagner: None. N.B. Prince: None. M.F. Hirshman: None. L.J. Goodyear: None.