Accumulating evidence suggests that obesity is related to immune dysfunction. Of particular interest, recent findings demonstrate that mice lacking either of two cellular adhesion receptors, ICAM-1 or Mac-1 (CD11b), exhibit reduced energy expenditure and obesity. ICAM-1 is expressed as multiple isoforms in many cell types and is required for leukocyte transendothelial migration. Mac-1 is a leukocyte-specific 2 integrin which is also essential for leukocyte migration and activation. Our hypothesis is that the obesity phenotype of these mice is due to disrupted intercellular events within adipose tissue. Specifically, that macrophages within adipose secrete cytokines that modulate lipid metabolism in nearby adipocytes, and that ICAM-1 and Mac-1 are required for this process through their influence on macrophage migration and activation. To test our hypothesis, we propose the following aims: 1) Determine if mice lacking all isoforms of ICAM-1 exhibit alterations in fat deposition or energy expenditure, 2) Determine the localization of macrophages within adipose tissue in normal, ICAM-1/- and Mac-1/- mice, relative to ICAM-1, Mac-1 and cytokine expression, and 3) Determine the effects of macrophage-derived cytokines on lipid metabolism and differentiation of adipocytes.
| Brake, Danett K; Smith, E O'Brian; Mersmann, Harry et al. (2006) ICAM-1 expression in adipose tissue: effects of diet-induced obesity in mice. Am J Physiol Cell Physiol 291:C1232-9 |
| Robker, Rebecca L; Collins, Robert G; Beaudet, Arthur L et al. (2004) Leukocyte migration in adipose tissue of mice null for ICAM-1 and Mac-1 adhesion receptors. Obes Res 12:936-40 |
