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(The FASEB Journal. 1998;12:57-65.)
© 1998 FASEB

RESEARCH COMMUNICATION

Leptin regulates proinflammatory immune responses

S. Loffredaa, S. Q. Yanga, H. Z. Lina, C. L. Karpa,b, M. L. Brengmanc, D. J. Wangd, A. S. Kleinc, G. B. Bulkleyc, C. Baoa, P. W. Noblea, M. D. Laned, and A. M. Diehla,1

a Department of Medicine, Johns Hopkins University, Baltimore, Maryland 21205, USA
b Department of Molecular Microbiology and Immunology, Johns Hopkins University, Baltimore, Maryland 21205, USA
c Department of Surgery, Johns Hopkins University, Baltimore, Maryland 21205, USA
d Department of Biological Chemistry, Johns Hopkins University, Baltimore, Maryland 21205, USA

Obesity is associated with an increased incidence of infection, diabetes, and cardiovascular disease, which together account for most obesity-related morbidity and mortality. Decreased expression of leptin or of functional leptin receptors results in hyperphagia, decreased energy expenditure, and obesity. It is unclear, however, whether defective leptin-dependent signal transduction directly promotes any of the conditions that frequently complicate obesity. Abnormalities in tumor necrosis factor {alpha} expression have been noted in each of the above comorbid conditions, so leptin deficiency could promote these complications if leptin had immunoregulatory activity. Studies of rodents with genetic abnormalities in leptin or leptin receptors revealed obesity-related deficits in macrophage phagocytosis and the expression of proinflammatory cytokines both in vivo and in vitro. Exogenous leptin up-regulated both phagocytosis and the production of proinflammatory cytokines. These results identify an important and novel function for leptin: up-regulation of inflammatory immune responses, which may provide a common pathogenetic mechanism that contributes to several of the major complications of obesity.—Loffreda, S., Yang, S. Q., Lin, H. Z., Karp, C. L., Brengman, M. L., Wang, D. J., Klein, A. S., Bulkley, G. B., Bao, C., Noble, P. W., Lane, M. D., Diehl, A. M. Leptin regulates proinflammatory immune responses. FASEB J. 12, 57–65 (1998)


Key Words: obesity • macrophage • cytokine • phagocytic function • TNF • lipopolysaccharide




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