title: Obesity-induced hyperleptinemia improves survival and immune response in a murine model of sepsis.
abstract: BACKGROUND
  Obesity is a growing health problem and associated with immune dysfunction. Sepsis is defined as systemic inflammatory response syndrome that occurs during infection. Excessive inflammation combined with immune dysfunction can lead to multiorgan damage and death.
  
  
  METHODS
  The authors investigated the influence of a class 1 obesity (body mass index between 30 and 34.9) on immune function and outcome in sepsis and the role of leptin on the immune response. The authors used a long-term high-fat-diet feeding model (12 weeks) on C57Bl/6 mice (n = 100) and controls on standard diet (n = 140) followed by a polymicrobial sepsis induced by cecal ligation and puncture.
  
  
  RESULTS
  The authors show that class 1 obesity is connected to significant higher serum leptin levels (data are mean ± SEM) (5.7 ± 1.2 vs. 2.7 ± 0.2 ng/ml; n = 5; P = 0.033) and improved innate immune response followed by significant better survival rate in sepsis (71.4%, n = 10 vs. 10%, n = 14; P < 0.0001). Additional sepsis-induced increases in leptin levels stabilize body temperature and are associated with a controlled immune response in a time-dependent and protective manner. Furthermore, leptin treatment of normal-weight septic mice with relative hypoleptinemia (n = 35) also significantly stabilizes body temperature, improves cellular immune response, and reduces proinflammatory cytokine response resulting in improved survival (30%; n = 10).
  
  
  CONCLUSIONS
  Relative hyperleptinemia of class 1 obesity or induced by treatment is protective in sepsis. Leptin seems to play a regulatory role in the immune system in sepsis, and treatment of relative hypoleptinemia could offer a new way of an individual sepsis therapy.
authors.affiliation: From the Department of Anaesthesiology, Ludwig Maximilian University of Munich, Munich, Germany (T.A., C.S., A.M., P.C., J.T.); Department of General and Visceral Surgery, University Hospital of Ulm, Ulm, Germany (N.H.); Division of Research, Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, Ohio (B.L.J., C.C.C.); and Walter-Brendel-Centre of Experimental Medicine, Ludwig-Maximilians-University Munich, Munich, Germany (D.S.).
authors.forename: Daniel
authors.initials: D
authors.lastname: Siegl
authors.forename: Thorsten
authors.initials: T
authors.lastname: Annecke
authors.forename: Bobby L
authors.initials: BL
authors.lastname: Johnson
authors.forename: Christian
authors.initials: C
authors.lastname: Schlag
authors.forename: Andre
authors.initials: A
authors.lastname: Martignoni
authors.forename: Nadine
authors.initials: N
authors.lastname: Huber
authors.forename: Peter
authors.initials: P
authors.lastname: Conzen
authors.forename: Charles C
authors.initials: CC
authors.lastname: Caldwell
authors.forename: Johannes
authors.initials: J
authors.lastname: Tschöp
mesh_terms: D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D001992:Bronchoalveolar Lavage Fluid; D002432:Cecum / Q000293:injuries / Q000502:physiology; D015169:Colony Count, Microbial; D016207:Cytokines / Q000378:metabolism; D004041:Dietary Fats / Q000494:pharmacology; D004435:Eating / Q000502:physiology; D005434:Flow Cytometry; D007111:Immunity, Cellular; D007249:Inflammation / Q000473:pathology; D007274:Injections, Intraperitoneal; D020738:Leptin / Q000008:administration & dosage / Q000097:blood* / Q000494:pharmacology; D007958:Leukocyte Count; D008026:Ligation; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000187:drug effects; D009765:Obesity / Q000378:metabolism*; D016897:Respiratory Burst / Q000187:drug effects; D018805:Sepsis / Q000276:immunology* / Q000382:microbiology / Q000401:mortality; D013534:Survival
chemical_list: D016207:Cytokines; D004041:Dietary Fats; D020738:Leptin