title: CD14 deficiency impacts glucose homeostasis in mice through altered adrenal tone.
abstract: The toll-like receptors comprise one of the most conserved components of the innate immune system, signaling the presence of molecules of microbial origin. It has been proposed that signaling through TLR4, which requires CD14 to recognize bacterial lipopolysaccharide (LPS), may generate low-grade inflammation and thereby affect insulin sensitivity and glucose metabolism. To examine the long-term influence of partial innate immune signaling disruption on glucose homeostasis, we analyzed knockout mice deficient in CD14 backcrossed into the diabetes-prone C57BL6 background at 6 or 12 months of age. CD14-ko mice, fed either normal or high-fat diets, displayed significant glucose intolerance compared to wild type controls. They also displayed elevated norepinephrine urinary excretion and increased adrenal medullary volume, as well as an enhanced norepinephrine secretory response to insulin-induced hypoglycemia. These results point out a previously unappreciated crosstalk between innate immune- and sympathoadrenal- systems, which exerts a major long-term effect on glucose homeostasis.
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.
authors.forename: James L
authors.initials: JL
authors.lastname: Young
authors.forename: Alfonso
authors.initials: A
authors.lastname: Mora
authors.forename: Anna
authors.initials: A
authors.lastname: Cerny
authors.forename: Michael P
authors.initials: MP
authors.lastname: Czech
authors.forename: Bruce
authors.initials: B
authors.lastname: Woda
authors.forename: Evelyn A
authors.initials: EA
authors.lastname: Kurt-Jones
authors.forename: Robert W
authors.initials: RW
authors.lastname: Finberg
authors.forename: Silvia
authors.initials: S
authors.lastname: Corvera
mesh_terms: D050154:Adiposity / Q000187:drug effects; D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004041:Dietary Fats / Q000494:pharmacology; D005215:Fasting / Q000097:blood; D005227:Fatty Acids / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D007003:Hypoglycemia / Q000097:blood / Q000473:pathology / Q000503:physiopathology; D007328:Insulin / Q000097:blood; D008055:Lipids / Q000097:blood; D018950:Lipopolysaccharide Receptors / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D004041:Dietary Fats; D005227:Fatty Acids; D007328:Insulin; D008055:Lipids; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D005947:Glucose