|Smith, C wayne|
Submitted to: American Journal of Physiology - Cell Physiology
Publication Type: Peer reviewed journal
Publication Acceptance Date: 6/5/2006
Publication Date: 12/1/2006
Citation: Brake, D.K., Smith, E.O., Mersmann, H.J., Smith, C.W., Robker, R.L. 2006. ICAM-1 expression in adipose tissue: Effects of diet-induced obesity in mice. American Journal of Physiology Cell Physiology. 291(6):C1232-1239. Interpretive Summary: Using a mouse model of dietary obesity, we examined the adipose tissue at 3 weeks and 6 months after starting the animals on a 20% milk fat diet rich in saturated fatty acids. The studies demonstrated that as early as 3 weeks, the adipose tissue developed inflammatory changes with the accumulation of activated white blood cells and the activation of genes that produce proinflammatory factors such as ICAM-1, an adhesion molecule known to assist in the formation of inflammatory lesions in arteries and liver. This proinflammatory state was evident in male mice but not female mice at 3 weeks, but by 6 months both male and female animals were affected. This study is an important demonstration of sex differences in response to an obesigenic diet and the production of a proinflammatory factor, ICAM-1, that may contribute to the inflammatory complications of obesity.
Technical Abstract: Obesity has been linked to cardiovascular disease, hypertension, diabetes, and metabolic syndrome with elevated markers of systemic inflammation. Intercellular adhesion molecule-1 (ICAM-1) is a transmembrane adhesion molecule involved in leukocyte migration to sites of inflammation. In human obesity elevations in the soluble form of ICAM-1 (sICAM-1) are positively correlated with abdominal fat deposition. Increases in adiposity have also been correlated with macrophage infiltration into adipose tissue. Here we investigate adipose tissue production and transcriptional regulation of ICAM-1 in a mouse model of dietary obesity. After feeding a high fat diet, ICAM-1 in serum and adipose tissue was analysed by ELISA, Northern blot, real-time quantitative PCR, and flow cytometry. After 6 months on the high fat diet, sICAM-1 levels significantly correlated with body weight and abdominal fat mass. ICAM-1 mRNA was expressed in adipose tissue of mice with significantly higher levels in males than females. After only 3 weeks there was an adipose tissue-specific increase in mRNA for ICAM-1, IL-6 and MCP-1 in male mice. Analysis of the stromal vascular fraction of male adipose tissue revealed CD11b negative cells with increased surface ICAM-1 and CD34. We also found two populations of F4/80+, CD11b+, ICAM-1+ cells, one of which also expressed CD14 and CD11c and was increased in response to a high fat diet. These results indicate that within 3 weeks on a high fat diet male mice exhibited significant increases in proinflammatory factors and immune cell infiltration in adipose tissue that may represent links between obesity and its associated inflammatory complications.