This Article Full Text Full Text (PDF) All Versions of this Article: 146/5/2157    most recent Author Manuscript (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sennello, J. A. Articles by Fantuzzi, G. Search for Related Content PubMed PubMed Citation Articles by Sennello, J. A. Articles by Fantuzzi, G.

Regulation of T Cell-Mediated Hepatic Inflammation by Adiponectin and Leptin

Divisions of Infectious Diseases (J.A.S., R.F., C.A.D., G.F.) and Endocrinology, Metabolism, and Diabetes (A.M.M., R.H.E.), University of Colorado Health Sciences Center, Denver, Colorado 80262; Rockefeller University (E.A., J.M., J.M.F.), New York, New York 10021; and Howard Hughes Medical Institute (J.M.F.), Chevy Chase, Maryland 20815

Address all correspondence and requests for reprints to: Dr. Giamila Fantuzzi, Department of Human Nutrition, University of Illinois, 1919 West Taylor Street, M/C 517, Chicago, Illinois 60612. E-mail: giamila{at}uic.edu.

Concanavalin A-induced hepatotoxicity was compared in lipodystrophic aP2-nSREBP-1c transgenic mice (LD mice) lacking adipose tissue, obese leptin-deficient ob/ob mice, and lean wild-type (WT) mice. Serum leptin and adiponectin were low in LD mice, whereas ob/ob mice had undetectable leptin, but high adiponectin. Protection from hepatotoxicity was observed in ob/ob, but not in LD mice, despite low cytokine levels and reduced T cell activation and hepatic natural killer T cells in both groups. Administration of adiponectin protected LD mice from hepatotoxicity without altering cytokine levels. In contrast, administration of leptin heightened disease susceptibility by restoring cytokine production. Neutralization of TNF protected LD mice from liver damage. Increased in vivo susceptibility to the hepatotoxic effect of TNF was observed in LD mice. In vitro, adiponectin protected primary hepatocytes from TNF-induced death, whereas leptin had no protective effect. In conclusion, although leptin increases susceptibility to hepatotoxicity by regulating cytokine production and T cell activation, adiponectin protects hepatocytes from TNF-induced death.

This article has been cited by other articles:

				M. Pini, M. E. Gove, J. A. Sennello, J. W. P. M. van Baal, L. Chan, and G. Fantuzzi Role and Regulation of Adipokines during Zymosan-Induced Peritoneal Inflammation in Mice Endocrinology, August 1, 2008; 149(8): 4080 - 4085. [Abstract] [Full Text] [PDF]

				N. Stefanou, M. Satra, V. Papanikolaou, F. Kalala, N. Gatselis, A. Germenis, G. N. Dalekos, and A. Tsezou Leptin receptor isoforms mRNA expression in peripheral blood mononuclear cells from patients with chronic viral hepatitis. Experimental Biology and Medicine, November 1, 2006; 231(10): 1653 - 1663. [Abstract] [Full Text] [PDF]

				M. Pini, J. A. Sennello, L. Chan, and G. Fantuzzi Adiponectin Deficiency Does Not Affect the Inflammatory Response to Endotoxin or Concanavalin A in Mice Endocrinology, November 1, 2006; 147(11): 5019 - 5022. [Abstract] [Full Text] [PDF]

				H. Laivuori, M.J. Gallaher, L. Collura, W.R. Crombleholme, N. Markovic, A. Rajakumar, C.A. Hubel, J.M. Roberts, and R.W. Powers Relationships between maternal plasma leptin, placental leptin mRNA and protein in normal pregnancy, pre-eclampsia and intrauterine growth restriction without pre-eclampsia Mol. Hum. Reprod., September 1, 2006; 12(9): 551 - 556. [Abstract] [Full Text] [PDF]

				K.-y. Kim, J. K. Kim, S. H. Han, J.-S. Lim, K. I. Kim, D. H. Cho, M.-S. Lee, J.-H. Lee, D.-Y. Yoon, S. R. Yoon, et al. Adiponectin Is a Negative Regulator of NK Cell Cytotoxicity J. Immunol., May 15, 2006; 176(10): 5958 - 5964. [Abstract] [Full Text] [PDF]

				C.-H. Lee, Y.-G. Chen, J. Chen, P. C. Reifsnyder, D. V. Serreze, M. Clare-Salzler, M. Rodriguez, C. Wasserfall, M. A. Atkinson, and E. H. Leiter Novel Leptin Receptor Mutation in NOD/LtJ Mice Suppresses Type 1 Diabetes Progression: II. Immunologic Analysis Diabetes, January 1, 2006; 55(1): 171 - 178. [Abstract] [Full Text] [PDF]

				C. W. Wieland, S. Florquin, E. D. Chan, J. C. Leemans, S. Weijer, A. Verbon, G. Fantuzzi, and T. van der Poll Pulmonary Mycobacterium tuberculosis infection in leptin-deficient ob/ob mice Int. Immunol., November 1, 2005; 17(11): 1399 - 1408. [Abstract] [Full Text] [PDF]

				L. A. Adams, P. Angulo, and K. D. Lindor Nonalcoholic fatty liver disease Can. Med. Assoc. J., September 27, 2005; 173(7): 735 - 735. [Full Text] [PDF]

				J. P. McGillis White Adipose Tissue, Inert No More! Endocrinology, May 1, 2005; 146(5): 2154 - 2156. [Full Text] [PDF]