Submitted to: Obesity Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/31/2004
Publication Date: 6/1/2004
Citation: Robker, R.L., Collins, R.G., Beaudet, A.L., Mersmann, H.J., Smith, W.C. 2004. Leukocyte migration in adipose tissue of mice null for ICAM-1 and Mac-1 adhesion receptors. Obesity Research. 12(6):936-940. Interpretive Summary: Obesity, a condition which places a person at risk for many adverse health consequences, has reached epidemic proportions among children in the United States. Although there has been increasing evidence of a link between the body's immune regulators and body weight, little is known about the fat tissue population of leukocytes, which are white blood cells that digest bacteria and are a vital part of the immune system. Cellular adhesion receptors (which control how immune cells stick to the layer of cells lining the blood vessels and then move into tissue) have been reported to be involved in the onset of obesity. Specifically, mice lacking either Mac-1 or ICAM-1 showed increased obesity in response to a high-fat diet compared to regular mice. The increased obesity was due to increased fat pad weight, and was not associated with increased food intake. This raises intriguing questions about links between immune dysfunction and obesity. In this study, we looked for such connections in our analysis of the leukocytes in the fat tissue pads of male and female mutant mice lacking both Mac-1 and ICAM-1. Our results show that leukocytes are a prevalent cell type in fat tissue. We also found great differences between male and female fat pads with regard to the number of leukocytes. The females' fat tissue pads contained many more macrophages, which are large, long-lived cells, than the males' fat tissue pads. However, our results also showed that leukocyte migration and fat metabolism do not depend on expression of ICAM-1 or Mac-1. In other words, they do not appear to be essential for fat tissue function, since our mutant mice did not show any changes in fat tissue deposition or fat cell metabolism. Our results differ from those of previous studies which showed increased obesity in such mutants. Thus, our findings underscore the importance of further evaluating white blood cell populations within fat tissue, to look for flags indicating links between obesity and immune function or dysfunction. Our study contributes to the improvement of children's nutrition because it provides valuable, new, gender-specific information about immune system regulators within fat tissue, which furthers research work toward understanding and controlling the epidemic of pediatric obesity.
Technical Abstract: To determine whether the leukocyte adhesion receptors ICAM-1 and Mac-1, regulators of immune cell migration, have an intrinsic role within adipose tissue by 1) analyzing the expression of ICAM-1 in adipose tissue, 2) identifying leukocyte populations within adipose tissue, and 3) determining whether ICAM-1 and Mac-1 mutant mice exhibit abnormal numbers of adipose tissue leukocytes. Wild-type, ICAM-1(-/-), and Mac-1(-/-) mice were fed a long-term high-fat diet. ICAM-1 expression was analyzed by Northern blot and immunohistochemistry. Leukocytes within adipose tissue were identified by immunohistochemistry and flow cytometry. ICAM-1 was expressed in adipose tissue and localized to the vascular endothelium. Macrophages and lymphocytes were prevalent within the stromal-vascular cell fraction of adipose tissue, and gender-specific differences were observed, with adipose tissue from female mice containing significantly more macrophages than tissue from male mice. Numbers of leukocytes in ICAM-1(-/-) and Mac-1(-/-) mice were not different from wild-types, however, indicating that these adhesion receptors are not required for leukocyte migration into adipose tissue. Our results documented leukocyte populations within adipose tissue, which may be involved in the development of heightened inflammation that is characteristic of obesity.