No evidence for a role of adipose tissue-derived serum amyloid a in the development of insulin resistance or obesity-related inflammation in hSAA1(+/-) transgenic mice

Abstract

Obesity is associated with a low-grade inflammation including moderately increased serum levels of the acute phase protein serum amyloid A (SAA). In obesity, SAA is mainly produced from adipose tissue and serum levels of SAA are associated with insulin resistance. SAA has been described as a chemoattractant for inflammatory cells and adipose tissue from obese individuals contains increased numbers of macrophages. However, whether adipose tissue-derived SAA can have a direct impact on macrophage infiltration in adipose tissue or the development of insulin resistance is unknown. The aim of this study was to investigate the effects of adipose tissue-derived SAA1 on the development of insulin resistance and obesity-related inflammation. We have previously established a transgenic mouse model expressing human SAA1 in the adipose tissue. For this report, hSAA1(+/-) transgenic mice and wild type mice were fed with a high fat diet or normal chow. Effects of hSAA1 on glucose metabolism were assessed using an oral glucose tolerance test. Real-time PCR was used to measure the mRNA levels of macrophage markers and genes related to insulin sensitivity in adipose tissue. Cytokines during inflammation were analyzed using a Proinflammatory 7-plex Assay. We found similar insulin and glucose levels in hSAA1 mice and wt controls during an oral glucose tolerance test and no decrease in mRNA levels of genes related to insulin sensitivity in adipose tissue in neither male nor female hSAA1 animals. Furthermore, serum levels of proinflammatory cytokines and mRNA levels of macrophage markers in adipose tissue were not increased in hSAA1 mice. Hence, in this model we find no evidence that adipose tissue-derived hSAA1 influences the development of insulin resistance or obesity-related inflammation.

Figure 1. Animal growth curves.

Growth curves for male hSAA1 mice (filled squares) and wt mice (open circles) fed either with a HFD (solid line) or NC (dashed line) for 12 weeks. n = 8–10 per group.

Figure 2. Levels of blood glucose and blood insulin during an oral glucose tolerance test.

A) Blood glucose levels during an oral glucose tolerance test in male wt mice (open circles) and male hSAA1 mice (filled squares) fed with HFD. B) Blood glucose area under the curve (AUC) in male mice fed with HFD. C) Blood insulin levels during oral glucose tolerance test in male wt mice (open circles) and male hSAA1 mice (filled squares) fed with HFD. D) Blood insulin area under the curve (AUC) in male mice fed with HFD. n = 9–10 per group.

Figure 3. Adipose tissue mRNA levels of genes related to insulin sensitivity.

mRNA levels of insulin sensitivity-related genes in (A) the gonadal fat depot and (B) the retroperitoneal fat depot in male mice. n = 8–10 per group. *indicates p<0.05, **p<0.01 and ***p<0.001.

Figure 4. Adipose tissue mRNA levels of macrophage markers.

mRNA levels of macrophage markers in (A) the gonadal fat depot and (B) the retroperitoneal fat depot in male mice. n = 8–10 per group. *indicates p<0.05, **p<0.01 and ***p<0.001.