Obesity and ethnicity alter gene expression in skin

Jeanne M Walker, Sandra Garcet, Jose O Aleman, Christopher E Mason, David Danko, Daniel Butler, Simone Zuffa, Jonathan R Swann, James Krueger, Jan L Breslow, Peter R Holt, Jeanne M Walker, Sandra Garcet, Jose O Aleman, Christopher E Mason, David Danko, Daniel Butler, Simone Zuffa, Jonathan R Swann, James Krueger, Jan L Breslow, Peter R Holt

Abstract

Obesity is accompanied by dysfunction of many organs, but effects on the skin have received little attention. We studied differences in epithelial thickness by histology and gene expression by Affymetrix gene arrays and PCR in the skin of 10 obese (BMI 35-50) and 10 normal weight (BMI 18.5-26.9) postmenopausal women paired by age and ethnicity. Epidermal thickness did not differ with obesity but the expression of genes encoding proteins associated with skin blood supply and wound healing were altered. In the obese, many gene expression pathways were broadly downregulated and subdermal fat showed pronounced inflammation. There were no changes in skin microbiota or metabolites. African American subjects differed from European Americans with a trend to increased epidermal thickening. In obese African Americans, compared to obese European Americans, we observed altered gene expression that may explain known differences in water content and stress response. African Americans showed markedly lower expression of the gene encoding the cystic fibrosis transmembrane regulator characteristic of the disease cystic fibrosis. The results from this preliminary study may explain the functional changes found in the skin of obese subjects and African Americans.

Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Consort flow chart of eligible subjects.
Figure 2
Figure 2
Differences in gene expression between the skin of obese and non-obese subjects. (A) Heat map of the 50 most differentially expressed genes in the skin of obese and non-obese subjects with an FCH (fold change) >  = 1.548; fdr (false discovery rate) <  = 0.1. (B) PCA (principal component analysis) plot of differentially expressed genes in the skin of obese and non-obese subjects with an FCH >  = 1.5; fdr < 0.1.
Figure 3
Figure 3
Differences in gene expression by RT- PCR between the skin of obese and non-obese subjects. LS means of gene expression by RT-PCR showing significant differences as *p < 0.05; **p < 0.01; ***p < 0.001.
Figure 4
Figure 4
Differences in gene expression between the subdermal fat of obese and non-obese subjects. (A) Heat map of the 50 most differentially expressed genes in subdermal fat of obese and non-obese subjects with an FCH >  = 1.5; fdr < 0.1. (B) PCA plot of differentially expressed genes in subdermal fat of obese and non-obese subjects with an FCH >  = 1.5; fdr < 0.1.
Figure 5
Figure 5
Differences in gene expression by RT-PCR between the subdermal fat of obese and non-obese subjects. LS means of gene expression by RT-PCR showing significant differences as *p < 0.05; **p < 0.01; ***p < 0.001.
Figure 6
Figure 6
Differences in gene expression between the skin of African American and European American subjects. (A) Heat map of the 50 most differentially expressed genes in skin of African American and European American subjects with an FCH >  = 1.5; fdr <  = 0.1. (B) PCA plot of differentially expressed genes in skin of obese and non-obese African American and European American subjects with an FCH = 1.5. Left side of plot indicates differences in gene expression by ethnicity in non-obese subjects. Right side of plot indicates differences in gene expression by ethnicity in obese subjects. (C) PCA plot of differentially expressed genes in skin of obese and non-obese subjects by ethnicity with an FCH = 1.5. Left side of plot indicates differences in gene expression between obese and non-obese African American subjects. Right side of plot indicates differences in gene expression between obese and non-obese European American subjects.
Figure 7
Figure 7
Differences in gene expression by RT- PCR between the skin of obese and non-obese African American and European American subjects. LS means of gene expression by RT-PCR showing significant differences as *p < 0.05; **p < 0.01; ***p < 0.001.
Figure 8
Figure 8
Differences in gene expression between the subdermal fat of African American and European American subjects. (A) Heat map of the 50 most differentially expressed genes in subdermal fat of African American and European American subjects with an FCH >  = 1.5; fdr <  = 0.1. (B) PCA plot of differentially expressed genes in subdermal fat of obese and non-obese African American and European American subjects with an FCH = 1.5. Left side of plot indicates differences in gene expression by race in non-obese subjects. Right side of plot indicates differences in gene expression by ethnicity in obese subjects. (C) PCA plot of differentially expressed genes in subdermal fat of obese and non-obese subjects by ethnicity with an FCH = 1.5. Left side of plot indicates differences in gene expression in obese and non-obese African American subjects. Right side of plot indicates differences in gene expression in obese and non-obese European American subjects.
Figure 9
Figure 9
Differences in gene expression by RT-PCR between the subdermal fat of obese and non-obese African American and obese and non-obese European American subjects. LS means of gene expression by RT-PCR showing significant differences as *p < 0.05; **p < 0.01; ***p < 0.001.
Figure 10
Figure 10
Metagenomic analysis of skin microbiomes. (A) PCA plot of taxonomic profiles for skin microbiomes from obese and non-obese subjects. (B) Total number of Antimicrobial Resistance Genes detected in samples (p = 0.1; Wilcox test).

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