Sepsis-induced intestinal microvascular and inflammatory responses in obese mice.
Although clinical obesity is associated with increases in the morbidity and mortality of sepsis, little is known about the mechanisms that underlie the influence of obesity on sepsis. The objective of this study was to determine (a) whether obesity is associated with exaggerated inflammatory and thrombogenic responses in the intestinal microvasculature of septic mice and (b) whether these microvascular alterations are related to changes in the serum levels of cytokines that are produced by adipose tissue. Intravital microscopy was used to quantify leukocyte and platelet adhesion in intestinal postcapillary venules of lean wild-type (WT) mice, and two murine models of obesity, that is, ob/ob and db/db mice. Sepsis was induced by cecal ligation and perforation (CLP). Serum cytokine levels were measured using a cytometric bead assay, whereas adipokines were quantified using enzyme-linked immunosorbent assay. Cecal ligation and perforation elicited significant increases in the adhesion of leukocytes and platelets in venules of lean WT mice. These CLP-induced adhesive interactions were much more pronounced in the microvasculature of both ob/ob and db/db mice. Cecal ligation and perforation was associated with significant increases in serum cytokines in both WT and ob/ob mice, but such changes were not detected in db/db mice. However, db/db (but not WT or ob/ob) mice did exhibit significant increases in serum leptin and adiponectin levels after CLP. Sepsis promotes more intense inflammatory and thrombogenic responses in the gut microcirculation of obese mice than in their lean counterparts. The obesity-enhanced microvascular dysfunction in septic mice shows no consistent correlation with serum cytokines or adipokines.
Singer
Georg
G
Department of Pediatric Surgery, Medical University of Graz, Graz, Austria.
Stokes
Karen Y
KY
Terao
Satoshi
S
Granger
D Neil
DN
D052242:Adiponectin / Q000097:blood; D000818:Animals; D001792:Blood Platelets / Q000378:metabolism / Q000382:microbiology; D002196:Capillaries / Q000378:metabolism / Q000473:pathology; D002448:Cell Adhesion; D016207:Cytokines / Q000097:blood; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000473:pathology / Q000503:physiopathology; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000098:blood supply* / Q000473:pathology; D020738:Leptin / Q000097:blood; D051379:Mice; D008820:Mice, Obese; D008833:Microcirculation; D009765:Obesity / Q000097:blood* / Q000473:pathology / Q000503:physiopathology; D010973:Platelet Adhesiveness; D018805:Sepsis / Q000097:blood* / Q000473:pathology / Q000503:physiopathology; D014699:Venules / Q000378:metabolism / Q000473:pathology
D052242:Adiponectin; D016207:Cytokines; D020738:Leptin