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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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L. Ottonello, P. Gnerre, M. Bertolotto, M. Mancini, P. Dapino, R. Russo, G. Garibotto, T. Barreca, and F. Dallegri
Leptin as a Uremic Toxin Interferes with Neutrophil Chemotaxis
J. Am. Soc. Nephrol., September 1, 2004; 15(9): 2366 - 2372.
[Abstract] [Full Text] [PDF]

Home page
 J. Nutr.Home page
S. D. Hursting, J. A. Lavigne, D. Berrigan, L. A. Donehower, B. J. Davis, J. M. Phang, J. C. Barrett, and S. N. Perkins
Diet-Gene Interactions in p53-Deficient Mice: Insulin-like Growth Factor-1 as a Mechanistic Target
J. Nutr., September 1, 2004; 134(9): 2482S - 2486S.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
P. Mancuso, C. Canetti, A. Gottschalk, P. K. Tithof, and M. Peters-Golden
Leptin augments alveolar macrophage leukotriene synthesis by increasing phospholipase activity and enhancing group IVC iPLA2 (cPLA2{gamma}) protein expression
Am J Physiol Lung Cell Mol Physiol, September 1, 2004; 287(3): L497 - L502.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
F. M. H. van Dielen, W. A. Buurman, M. Hadfoune, J. Nijhuis, and J. W. Greve
Macrophage Inhibitory Factor, Plasminogen Activator Inhibitor-1, Other Acute Phase Proteins, and Inflammatory Mediators Normalize as a Result of Weight Loss in Morbidly Obese Subjects Treated with Gastric Restrictive Surgery
J. Clin. Endocrinol. Metab., August 1, 2004; 89(8): 4062 - 4068.
[Abstract] [Full Text] [PDF]

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 Diabetes CareHome page
J. Medina, L. I. Fernandez-Salazar, L. Garcia-Buey, and R. Moreno-Otero
Approach to the Pathogenesis and Treatment of Nonalcoholic Steatohepatitis
Diabetes Care, August 1, 2004; 27(8): 2057 - 2066.
[Abstract] [Full Text] [PDF]

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 CirculationHome page
A. S.M. Shamsuzzaman, M. Winnicki, R. Wolk, A. Svatikova, B. G. Phillips, D. E. Davison, P. B. Berger, and V. K. Somers
Independent Association Between Plasma Leptin and C-Reactive Protein in Healthy Humans
Circulation, May 11, 2004; 109(18): 2181 - 2185.
[Abstract] [Full Text] [PDF]

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 DiabetesHome page
C. A. Curat, A. Miranville, C. Sengenes, M. Diehl, C. Tonus, R. Busse, and A. Bouloumie
From Blood Monocytes to Adipose Tissue-Resident Macrophages: Induction of Diapedesis by Human Mature Adipocytes
Diabetes, May 1, 2004; 53(5): 1285 - 1292.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Crit. Care Med.Home page
S. T. Weiss and S. Shore
Obesity and Asthma: Directions for Research
Am. J. Respir. Crit. Care Med., April 15, 2004; 169(8): 963 - 968.
[Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
C. J. Hukshorn, J. H. N. Lindeman, K. H. Toet, W. H. M. Saris, P. H. C. Eilers, M. S. Westerterp-Plantenga, and T. Kooistra
Leptin and the Proinflammatory State Associated with Human Obesity
J. Clin. Endocrinol. Metab., April 1, 2004; 89(4): 1773 - 1778.
[Abstract] [Full Text] [PDF]

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 J. Physiol.Home page
S. Gaige, E. Abou, A. Abysique, and M. Bouvier
Effects of interactions between interleukin-1{beta} and leptin on cat intestinal vagal mechanoreceptors
J. Physiol., February 15, 2004; 555(1): 297 - 310.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
Q. Cao, K. M. Mak, C. Ren, and C. S. Lieber
Leptin Stimulates Tissue Inhibitor of Metalloproteinase-1 in Human Hepatic Stellate Cells: RESPECTIVE ROLES OF THE JAK/STAT AND JAK-MEDIATED H2O2-DEPENDENT MAPK PATHWAYS
J. Biol. Chem., February 6, 2004; 279(6): 4292 - 4304.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
H. Bays, L. Mandarino, and R. A. DeFronzo
Role of the Adipocyte, Free Fatty Acids, and Ectopic Fat in Pathogenesis of Type 2 Diabetes Mellitus: Peroxisomal Proliferator-Activated Receptor Agonists Provide a Rational Therapeutic Approach
J. Clin. Endocrinol. Metab., February 1, 2004; 89(2): 463 - 478.
[Full Text] [PDF]

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 Recent Prog Horm ResHome page
K. Rahmouni and W. G. Haynes
Leptin and the Cardiovascular System
Recent Prog. Horm. Res., January 1, 2004; 59(1): 225 - 244.
[Abstract] [Full Text]

Home page
 Exp. Biol. Med.Home page
H. Utsumi, R. Iwakiri, B. Wu, T. Fujise, H. Sakata, R. Shimoda, S. Amemori, S. Tsunada, A. Ootani, and K. Fujimoto
Intracerebroventricular Administration of Leptin-Induced Apoptosis in the Rat Small Intestinal Mucosa
Experimental Biology and Medicine, November 1, 2003; 228(10): 1239 - 1244.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
N. K. Ryan, K. H. Van der Hoek, S. A. Robertson, and R. J. Norman
Leptin and Leptin Receptor Expression in the Rat Ovary
Endocrinology, November 1, 2003; 144(11): 5006 - 5013.
[Abstract] [Full Text] [PDF]

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 J. Histochem. Cytochem.Home page
M. Archanco, F. J. Muruzabal, D. Llopiz, M. Garayoa, J. Gomez-Ambrosi, G. Fruhbeck, and M. A. Burrell
Leptin Expression in the Rat Ovary Depends on Estrous Cycle
J. Histochem. Cytochem., October 1, 2003; 51(10): 1269 - 1277.
[Abstract] [Full Text] [PDF]

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 J. Am. Coll. Nutr.Home page
L. M. Gaetke, H. S. Oz, R. C. Frederich, and C. J. McClain
Anti-TNF-{alpha} Antibody Normalizes Serum Leptin in IL-2 Deficient Mice
J. Am. Coll. Nutr., October 1, 2003; 22(5): 415 - 420.
[Abstract] [Full Text] [PDF]

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 Ann Rheum DisHome page
G Palmer and C Gabay
A role for leptin in rheumatic diseases?
Ann Rheum Dis, October 1, 2003; 62(10): 913 - 915.
[Full Text]

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 J. Appl. Physiol.Home page
S. A. Shore, Y. M. Rivera-Sanchez, I. N. Schwartzman, and R. A. Johnston
Responses to ozone are increased in obese mice
J Appl Physiol, September 1, 2003; 95(3): 938 - 945.
[Abstract] [Full Text] [PDF]

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 DiabetesHome page
F. Maingrette and G. Renier
Leptin Increases Lipoprotein Lipase Secretion by Macrophages: Involvement of Oxidative Stress and Protein Kinase C
Diabetes, August 1, 2003; 52(8): 2121 - 2128.
[Abstract] [Full Text] [PDF]

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 ThoraxHome page
D D Sin and S F P Man
Impaired lung function and serum leptin in men and women with normal body weight: a population based study
Thorax, August 1, 2003; 58(8): 695 - 698.
[Abstract] [Full Text] [PDF]

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 Infect. Immun.Home page
S. I. Moore, G. B. Huffnagle, G.-H. Chen, E. S. White, and P. Mancuso
Leptin Modulates Neutrophil Phagocytosis of Klebsiella pneumoniae
Infect. Immun., July 1, 2003; 71(7): 4182 - 4185.
[Abstract] [Full Text] [PDF]

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 Biol. Reprod.Home page
G. K. Bhat, M. L. Hamm, J. U. Igietseme, and D. R. Mann
Does Leptin Mediate the Effect of Photoperiod on Immune Function in Mice?
Biol Reprod, July 1, 2003; 69(1): 30 - 36.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
N. Pannacciulli, R. Vettor, G. Milan, M. Granzotto, A. Catucci, G. Federspil, P. De Giacomo, R. Giorgino, and G. De Pergola
Anorexia Nervosa Is Characterized by Increased Adiponectin Plasma Levels and Reduced Nonoxidative Glucose Metabolism
J. Clin. Endocrinol. Metab., April 1, 2003; 88(4): 1748 - 1752.
[Abstract] [Full Text] [PDF]

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 Mol Hum ReprodHome page
R. R. Gonzalez, K. Leary, J. C. Petrozza, and P. C. Leavis
Leptin regulation of the interleukin-1 system in human endometrial cells
Mol. Hum. Reprod., March 1, 2003; 9(3): 151 - 158.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
M. Halle and P. B. Persson
Role of leptin and leptin receptor in inflammation
Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2003; 284(3): R760 - R762.
[Full Text] [PDF]

Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
A. M. Madiehe, T. D. Mitchell, and R. B. S. Harris
Hyperleptinemia and reduced TNF-alpha secretion cause resistance of db/db mice to endotoxin
Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2003; 284(3): R763 - R770.
[Abstract] [Full Text] [PDF]

Home page
 Exp. Biol. Med.Home page
U. N. Das
Is Metabolic Syndrome X an Inflammatory Condition?
Experimental Biology and Medicine, December 1, 2002; 227(11): 989 - 997.
[Abstract] [Full Text]

Home page
 Arch. Dis. Child.Home page
S E Moore, G Morgan, A C Collinson, J A Swain, M A O'Connell, and A M Prentice
Leptin, malnutrition, and immune response in rural Gambian children
Arch. Dis. Child., September 1, 2002; 87(3): 192 - 197.
[Abstract] [Full Text] [PDF]

Home page
 J. Physiol.Home page
S. Gaige, A. Abysique, and M. Bouvier
Effects of leptin on cat intestinal vagal mechanoreceptors
J. Physiol., September 1, 2002; 543(2): 679 - 689.
[Abstract] [Full Text] [PDF]

Home page
 J. Leukoc. Biol.Home page
G. M. Lord, G. Matarese, J. K. Howard, S. R. Bloom, and R. I. Lechler
Leptin inhibits the anti-CD3-driven proliferation of peripheral blood T cells but enhances the production of proinflammatory cytokines
J. Leukoc. Biol., August 1, 2002; 72(2): 330 - 338.
[Abstract] [Full Text] [PDF]


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