Abstract 10396: The Lack of CD4-Positive Lymphocytes Attenuates Glucose Intolerance in Mice
Background: In obesity, low grade adipose tissue inflammation is a key process underlying insulin resistance (IR). Recent animal studies suggest CD4-positive lymphocytes to be involved. However, the causal role of these cells is still to be determined. Therefore the present study examined the development of diet induced IR in a mouse model lacking CD4-positive lymphocytes.
Results: MHC class II knock-out mice (KO) which possess only 1–2% of the normal CD4-positve lymphocyte content were used. Wild-type (WT) and KO mice were fed a high fat diet (HFD) for 10 weeks. Weight gain and food intake were similar. KO mice were significantly less glucose intolerant compared to WT mice (118.8±2.7 and 135.0±7.4% compared to baseline respectively, p<0.05). Insulin resistance was similar in both groups (KO: 27.8±9.7%, WT: 25.3±7.4% compared to baseline, p=0.4). Serum analysis revealed similar glucose and insulin levels in KO and WT mice (Glucose: 253.2±11.3 and 248.1±12.77mg/dl; Insulin: 0.87±0.17 and 0.85±0.26ng/ml respectively). In contrast, triglyceride levels were higher and cholesterol levels lower in KO compared to WT mice (triglyceride: 16.9±1.4 and 26.7±4.2mg/dl respectively; cholesterol: 105.6±3.5 and 88.2±6.7mg/dl respectively; p<0.05). Real time PCR analysis of epididymal adipose tissue showed a significantly lower macrophage content in KO compared to WT mice (0.40±0.06 and 0.66±0.10 respectively, p<0.05), which was confirmed by immunohistochemistry. In contrast, KO mice have a higher lymphocyte content as determined by CD3 (0.74±0.07 and 0.56±0.03 respectively, p<0.05), which was found to be due to a higher content of CD8-positive lymphocytes in the KO animals (0.60±0.058 and 0.14±0.01 respectively, p<0.0001). The T-lymphocyte cytokine RANTES was significantly higher in KO mice (0.65±0.06 and 0.33±0.04 respectively, p<0.001), whereas SDF-1α expression was not different.
Conclusion: Mice lacking CD4-positive lymphocytes develop attenuated glucose intolerance but unchanged insulin resistance which accompany with more T-lymphocytes and less macrophages in adipose tissue. These observations suggest that the balance of T-cells in adipose tissue may play an important role in adipose tissue inflammation and the development of IR.
- © 2010 by American Heart Association, Inc.