Leptin alters antibody isotype in the pig in vivo, but does not regulate cytokine expression or stimulate STAT3 signaling in peripheral blood monocytes in vitro.
Although leptin modulates immunological pathways in some species, the role of leptin as a regulator of immunocyte function in the pig has not been studied. Therefore, the primary objective of this study was to determine whether leptin influences specific immunocyte response variables in the pig in vivo or in vitro. Fifteen pigs (five pigs per treatment) were 1) injected with recombinant human leptin and allowed to consume feed ad libitum, 2) injected with vehicle and allowed to consume feed ad libitum, or 3) injected with vehicle and limit-fed to the intake of the leptin-injected group. All the pigs also were injected with the antigen, Limulus hemocyanin, on d 0 and 15 of the experiment. Exogenous leptin decreased (P < 0.05) daily feed intake and antigen-specific immunoglobulin (Ig) G1, but had no effect on lymphocyte proliferation or antigen-specific IgG2. In a second series of experiments, peripheral blood mononuclear cells (PBMC) were isolated from venous blood to determine the effect of stimulation with the polyclonal mitogen, concanavalin A (ConA), on the long form of the leptin receptor (Ob-Rl) mRNA abundance, and to determine whether leptin altered mitogen-induced proliferation, cytokine production, or signal transducer and activator of transcription 3 (STAT3) activation. Leptin had no effect on the proliferation of PBMC or on cytokine mRNA abundance or secretion. The abundance of Ob-Rl mRNA was decreased (P < 0.05) in response to stimulation with ConA. Constitutive STAT3 DNA binding was evident in mobility shift assays, but was not altered by either leptin or serum deprivation. These data indicate that leptin modifies antibody isotypes in the pig, and that Ob-Rl expression is downregulated in response to polyclonal mitogens in porcine PBMC. The constitutive activation of STAT3, coupled with the absence of leptin-inducible binding, indicates an alternative signaling pathway for leptin in pig PBMC.
Weber
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Department of Animal Sciences, Purdue University, West Lafayette, IN 47907, USA.
Spurlock
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D000818:Animals; D003208:Concanavalin A / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D004268:DNA-Binding Proteins / Q000502:physiology*; D004435:Eating; D005786:Gene Expression Regulation; D007074:Immunoglobulin G / Q000032:analysis* / Q000145:classification; D020738:Leptin / Q000097:blood / Q000502:physiology*; D008213:Lymphocyte Activation; D008297:Male; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D011956:Receptors, Cell Surface / Q000378:metabolism; D054411:Receptors, Leptin; D050796:STAT3 Transcription Factor; D015398:Signal Transduction; D013552:Swine / Q000097:blood / Q000235:genetics / Q000276:immunology*; D015534:Trans-Activators / Q000502:physiology*
D016207:Cytokines; D004268:DNA-Binding Proteins; D007074:Immunoglobulin G; C515448:LEPR protein, human; D020738:Leptin; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D050796:STAT3 Transcription Factor; D015534:Trans-Activators; D003208:Concanavalin A