Leptin causes body weight loss in the absence of in vivo activities typical of cytokines of the IL-6 family.

To investigate if leptin shares in vivo activities with interleukin (IL)-6 family cytokines, it was tested in normal mice for the ability, after a single injection, to induce the acute-phase protein serum amyloid A, to potentiate the induction by IL-1 of serum corticosterone and IL-6, and to inhibit the induction by lipopolysaccharide of serum tumor necrosis factor and, after seven daily injections, to cause body weight loss and to change peripheral blood cell counts. At a 0.5 mg/kg dose, leptin caused body weight loss but did not show any of the other activities above. At a dose of 5 mg/kg, which also caused body weight loss, leptin potentiated the induction by IL-1 of serum corticosterone and IL-6 but did not show any other activity. In addition to causing body weight loss, leptin shows only some of the in vivo activities typical of IL-6 family cytokines and only if used at a dose that exceeds the one sufficient to affect body weight. In vivo, leptin seems to chiefly control body weight and not inflammatory or hematopoietic processes.

[1]  E. Ravussin,et al.  Relationship of the white blood cell count to body fat: role of leptin , 1997, British journal of haematology.

[2]  T. Murakami,et al.  A short form of leptin receptor performs signal transduction. , 1997, Biochemical and biophysical research communications.

[3]  W. Alexander,et al.  Leptin can induce proliferation, differentiation, and functional activation of hemopoietic cells. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[4]  P. Ghezzi,et al.  Cardiotrophin-1 inhibits tumor necrosis factor production in the heart and serum of lipopolysaccharide-treated mice and in vitro in mouse blood cells. , 1996, The American journal of pathology.

[5]  L. Tartaglia,et al.  The full-length leptin receptor has signaling capabilities of interleukin 6-type cytokine receptors. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[6]  T. Murakami,et al.  Substitution at codon 269 (glutamine --> proline) of the leptin receptor (OB-R) cDNA is the only mutation found in the Zucker fatty (fa/fa) rat. , 1996, Biochemical and Biophysical Research Communications - BBRC.

[7]  R. Skoda,et al.  Defective STAT signaling by the leptin receptor in diabetic mice. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[8]  T. Murakami,et al.  Phenotype-linked amino acid alteration in leptin receptor cDNA from Zucker fatty (fa/fa) rat. , 1996, Biochemical and biophysical research communications.

[9]  A. Mikhail,et al.  Novel B219/OB receptor isoforms: Possible role of leptin in hematopoiesis and reproduction , 1996, Nature Medicine.

[10]  J. Friedman,et al.  Endotoxin and cytokines induce expression of leptin, the ob gene product, in hamsters. , 1996, The Journal of clinical investigation.

[11]  G. Fantuzzi,et al.  Six different cytokines that share GP130 as a receptor subunit, induce serum amyloid A and potentiate the induction of interleukin-6 and the activation of the hypothalamus-pituitary-adrenal axis by interleukin-1. , 1996, Blood.

[12]  B. Barton,et al.  Interleukins 6 and 11 protect mice from mortality in a staphylococcal enterotoxin-induced toxic shock model , 1996, Infection and immunity.

[13]  C. Plata-salamán.  Anorexia induced by activators of the signal transducer gp 130 , 1996, Neuroreport.

[14]  J. Friedman,et al.  Abnormal splicing of the leptin receptor in diabetic mice , 1996, Nature.

[15]  L. Tartaglia,et al.  Evidence That the Diabetes Gene Encodes the Leptin Receptor: Identification of a Mutation in the Leptin Receptor Gene in db/db Mice , 1996, Cell.

[16]  Rene Devos,et al.  Identification and expression cloning of a leptin receptor, OB-R , 1995, Cell.

[17]  Thomas Madej,et al.  Threading analysis suggests that the obese gene product may be a helical cytokine , 1995, FEBS letters.

[18]  S. Akira,et al.  Interleukin-6 family of cytokines and gp130. , 1995, Blood.

[19]  S. Burstein,et al.  Thrombocytopoietic properties of oncostatin M. , 1995, Blood.

[20]  M. Pelleymounter,et al.  Effects of the obese gene product on body weight regulation in ob/ob mice. , 1995, Science.

[21]  Steven L. Cohen,et al.  Weight-reducing effects of the plasma protein encoded by the obese gene. , 1995, Science.

[22]  W. Wood,et al.  Cardiotrophin-1 , 1995, The Journal of Biological Chemistry.

[23]  J. Williams,et al.  Intratracheal injection of LPS and cytokines. V. LPS induces expression of LIF and LIF inhibits acute inflammation. , 1994, The American journal of physiology.

[24]  G. Yancopoulos,et al.  LIFR beta and gp130 as heterodimerizing signal transducers of the tripartite CNTF receptor. , 1993, Science.

[25]  H. Broxmeyer,et al.  In vivo effects of recombinant interleukin-11 on myelopoiesis in mice. , 1993, Blood.

[26]  Comeau,et al.  The IL-6 signal transducer, gp130: an oncostatin M receptor and affinity converter for the LIF receptor. , 1992, Science.

[27]  D. Remick,et al.  Endotoxin-induced cytokine gene expression in vivo. III. IL-6 mRNA and serum protein expression and the in vivo hematologic effects of IL-6. , 1991, Journal of immunology.

[28]  D. Gearing,et al.  Effects of injected leukemia inhibitory factor on hematopoietic and other tissues in mice. , 1990, Blood.

[29]  J. Vilček,et al.  IL-6 inhibits lipopolysaccharide-induced tumor necrosis factor production in cultured human monocytes, U937 cells, and in mice. , 1989, Journal of immunology.

[30]  T. Hirano,et al.  Interleukin-6 is a potent thrombopoietic factor in vivo in mice. , 1989, Blood.

[31]  S. Rosenberg,et al.  In vivo induction of IL-6 by administration of exogenous cytokines and detection of de novo serum levels of IL-6 in tumor-bearing mice. , 1989, Journal of immunology.

[32]  A. Mantovani,et al.  IL-1 stimulates IL-6 production in endothelial cells. , 1989, Journal of immunology.

[33]  C. Uyttenhove,et al.  Purification and NH2-terminal amino acid sequence of a T-cell-derived lymphokine with growth factor activity for B-cell hybridomas. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[34]  Eric M. Smith,et al.  Corticotropin-releasing activity of monokines. , 1985, Science.

[35]  D. Goeddel,et al.  Human tumor necrosis factor. Production, purification, and characterization. , 1985, The Journal of biological chemistry.

[36]  M. Kaplan,et al.  Monokine-induced synthesis of serum amyloid A protein by hepatocytes , 1980, Nature.

[37]  G. Scurfield,et al.  Effects of 5‐Fluorouracil on Mouse Bone Marrow , 1979, British journal of haematology.

[38]  H. Snodgrass,et al.  Leptin stimulates fetal and adult erythroid and myeloid development. , 1997, Blood.

[39]  M. Maffei,et al.  Positional cloning of the mouse obese gene and its human homologue , 1995, Nature.

[40]  Gearing Dp,et al.  Oncostatin M binds the high-affinity leukemia inhibitory factor receptor. , 1992 .