A comparison of inflammatory and oxidative stress markers in adipose tissue from weight-matched obese male and female mice - PubMed (original) (raw)

Comparative Study

A comparison of inflammatory and oxidative stress markers in adipose tissue from weight-matched obese male and female mice

Karen J Nickelson et al. Exp Diabetes Res. 2012.

Abstract

Expansion of intra-abdominal adipose tissue and the accompanying inflammatory response has been put forward as a unifying link between obesity and the development of chronic diseases. However, an apparent sexual dimorphism exists between obesity and chronic disease risk due to differences in the distribution and abundance of adipose tissue. A range of experimental protocols have been employed to demonstrate the role of estrogen in regulating health benefits; however, most studies are confounded by significant differences in body weight and adiposity. Therefore, the purpose of this study was to compare weight-matched obese male and female mice to determine if the sex-dependent health benefits remain when body weight is similar. The development of obesity in female mice receiving a high-fat diet was delayed; however, subsequent comparisons of weight-matched obese mice revealed greater adiposity in obese female mice. Despite excess adiposity and enlarged adipocyte size, obese females remained more glucose tolerant than weight-matched male mice, and this benefit was associated with increased expression of adiponectin and reductions in immune cell infiltration and oxidative stress in adipose tissue. Therefore, the protective benefits of estrogen persist in the obese state and appear to improve the metabolic phenotype of adipose tissue and the individual.

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Figures

Figure 1

Figure 1

Obese female mice (female HFD) have improved glucose tolerance when compared to weight-matched obese male mice (male HFD). Male and female C57BL/6 mice were fed either a standard rodent chow or a high-fat diet (HFD) from 6 weeks of age until the HFD-fed group achieved a body weight of 45 g. At that time, a glucose tolerance test was performed in both chow- and HFD-fed males (21 weeks old) or females (38 weeks old) and blood glucose change over time plotted (a). Corresponding blood glucose area under the curve (AUC) was calculated (b), data are reported as mean ± SE and means with different superscripts differ by P < 0.05. n = 5–8 per group.

Figure 2

Figure 2

Adiponectin mRNA expression in gonadal adipose tissue is reduced by obesity in male mice but not weight-matched obese female mice. Male and female C57BL/6 mice were fed either a standard rodent chow or a high-fat diet (HFD) from 6 weeks of age until the HFD-fed group achieved a body weight of 45 g. At that time, both chow- and HFD-fed males (21 weeks old) or females (38 weeks old) were sacrificed and qRT PCR performed on gonadal adipose tissue. Relative mRNA expression of adiponectin was reduced by obesity in male mice, while obesity had no effect on adiponectin expression in female mice (a). Consistent with an obese phenotype, mRNA expression of leptin was elevated in both male HFD and female HFD mice (b). Data are reported as mean ± SE; n = 5–8 per group; means with different superscripts differ by P < 0.05.

Figure 3

Figure 3

Obese female mice have larger adipocytes and reduced prevalence of crown-like structures in gonadal adipose tissue when compared to weight-matched obese male mice. Male and female C57BL/6 mice were fed either a standard rodent chow or a high-fat diet (HFD) from 6 weeks of age until the HFD-fed group achieved a body weight of 45 g. At that time, both chow- and HFD-fed males (21 weeks old) or females (38 weeks old) were sacrificed and histological analysis was performed on gonadal adipose tissue. Representative H&E stains of gonadal adipose tissue from each of the four treatment groups are presented in panel (a). Sections were used to quantify the presence of crown-like structure (b) and to calculate average adipocyte area (c). Data are reported as mean ± SE; n = 5–8 per group; means with different superscripts differ by P < 0.05; *P < 0.05; bar = 100 _μ_M.

Figure 4

Figure 4

Relative mRNA expression of markers for immune cell infiltration and oxidative stress is decreased in gonadal adipose tissue isolated from obese female mice as compared to obese male mice. Male and female C57BL/6 mice were fed either a standard rodent chow or a high-fat diet (HFD) from 6 weeks of age until the HFD-fed group achieved a body weight of 45 g. At that time, both chow- and HFD-fed males (21 weeks old) or females (38 weeks old) were sacrificed and qRT PCR was performed on gonadal adipose tissue. Relative mRNA expression of markers for immune cell infiltration and inflammation (a) as well as oxidative stress (b) was determined. Data are reported as mean ± SE; n = 5–8 per group; means with different superscripts differ by P < 0.05. IL-6: interleukin-6; MCP-1: monocyte chemoattractant protein-1; TNF-α: tumor necrosis factor-alpha; eNOS: endothelial nitric oxide synthase; iNOS: inducible nitric oxide synthase; HO-1: heme oxygenase-1; p40phox: NADPH subunit p40phox; Prdx1: peroxiredoxin-1.

Figure 5

Figure 5

Relative mRNA expression of markers for immune cell infiltration and oxidative stress is altered in subcutaneous adipose tissue isolated from obese female mice as compared to obese male mice. Male and female C57BL/6 mice were fed either a standard rodent chow or a high-fat diet (HFD) from 6 weeks of age until the HFD-fed group achieved a body weight of 45 g. At that time, both chow- and HFD-fed males (21 weeks old) or females (38 weeks old) were sacrificed and qRT PCR was performed on subcutaneous adipose tissue. Relative mRNA expression of markers for immune cell infiltration and inflammation (a) as well as oxidative stress (b) was determined. Data are reported as mean ± SE; n = 5–8 per group; means with different superscripts differ by P < 0.05. IL-6: interleukin-6; MCP-1: monocyte chemoattractant protein-1; TNF-α: tumor necrosis factor-alpha; eNOS: endothelial nitric oxide synthase; iNOS: inducible nitric oxide synthase; HO-1: heme oxygenase-1; p40phox: NADPH subunit p40phox; Prdx1: peroxiredoxin-1.

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