Supplemental_Figures.pdf (4.63 MB)
Exercise Training Promotes Sex-Specific Adaptations in Mouse Inguinal White Adipose Tissue
figure
posted on 2021-02-10, 01:18 authored by Pasquale Nigro, Roeland J. W. Middelbeek, Christiano R. R. Alves, Susana Rovira–Llopis, Krithika Ramachandran, Leslie A. Rowland, Andreas B. Møller, Hirokazu Takahashi, Ana B. Alves-Wagner, Maria Vamvini, Nathan S. Makarewicz, Brent G. Albertson, Michael F. Hirshman, Laurie J. GoodyearRecent
studies demonstrate that adaptations to white adipose tissue are important components
of the beneficial effects of exercise training on metabolic health. Exercise
training favorably alters the phenotype of subcutaneous inguinal white adipose tissue (iWAT) in male mice including decreasing fat mass, improving
mitochondrial function, inducing beiging and stimulating the secretion of adipokines. Here, we find that despite performing
more voluntary wheel running compared to males, these adaptations do not occur
in the iWAT of female mice. Consistent with sex-specific adaptations, we report
that mRNA expression of androgen receptor co-activators are upregulated in iWAT
from trained male mice, and that testosterone treatment of primary adipocytes
derived from the iWAT of male, but not female mice, phenocopies exercise-induced
metabolic adaptations. Sex-specificity also occurs in the secretome profile, as
we identify Cysteine Rich Secretory Protein 1(Crisp1) as a novel adipokine
that is only secreted from male iWAT in response to exercise. Crisp1 expression is upregulated by
testosterone and functions to increase glucose and fatty acid uptake. Our finding that adaptations to iWAT with
exercise training are dramatically greater in male mice has potential clinical implications
for understanding the different metabolic response to exercise training in males
and females, and demonstrates the importance of investigating both sexes in
studies of adipose tissue biology.