Obesity-induced Hyperleptinemia Improves Survival and Immune Response in a Murine Model of Sepsis

• Published in: Anesthesiology (Philadelphia) Vol. 121; no. 1; pp. 98 - 114
• Main Authors: Siegl, Daniel, Annecke, Thorsten, Johnson, Bobby L, Schlag, Christian, Martignoni, Andre, Huber, Nadine, Conzen, Peter, Caldwell, Charles C, Tschöp, Johannes
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD American Society of Anesthesiologists, Inc 01-07-2014; Lippincott Williams & Wilkins
• Subjects: Anesthesia; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Bacterial diseases; Bacterial sepsis; Biological and medical sciences; Body Temperature - drug effects; Bronchoalveolar Lavage Fluid; Cecum - injuries; Cecum - physiology; Colony Count, Microbial; Cytokines - metabolism; Dietary Fats - pharmacology; Eating - physiology; Flow Cytometry; Human bacterial diseases; Immunity, Cellular; Infectious diseases; Inflammation - pathology; Injections, Intraperitoneal; Leptin - administration & dosage; Leptin - blood; Leptin - pharmacology; Leukocyte Count; Ligation; Medical sciences; Metabolic diseases; Mice; Mice, Inbred C57BL; Neutrophils - drug effects; Obesity; Obesity - metabolism; Respiratory Burst - drug effects; Sepsis - immunology; Sepsis - microbiology; Sepsis - mortality; Survival; Obesity; Immune response; Rodentia; Nutrition disorder; Survival; Bacteremia; Infection; Sepsis syndrome; Vertebrata; Improvement; Mammalia; Mouse; Animal; Bacteriosis; Anesthesia; Models; Nutritional status
• ISSN: 0003-3022; 1528-1175
• DOI: 10.1097/ALN.0000000000000192

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.