title: Surfactant protein d deficiency in mice is associated with hyperphagia, altered fat deposition, insulin resistance, and increased basal endotoxemia.
abstract: Pulmonary surfactant protein D (SP-D) is a host defence lectin of the innate immune system that enhances clearance of pathogens and modulates inflammatory responses. Recently it has been found that systemic SP-D is associated with metabolic disturbances and that SP-D deficient mice are mildly obese. However, the mechanism behind SP-D's role in energy metabolism is not known.Here we report that SP-D deficient mice had significantly higher ad libitum energy intake compared to wild-type mice and unchanged energy expenditure. This resulted in accumulation but also redistribution of fat tissue. Blood pressure was unchanged. The change in energy intake was unrelated to the basal levels of hypothalamic Pro-opiomelanocortin (POMC) and Agouti-related peptide (AgRP) gene expression. Neither short time systemic, nor intracereberoventricular SP-D treatment altered the hypothalamic signalling or body weight accumulation.In ad libitum fed animals, serum leptin, insulin, and glucose were significantly increased in mice deficient in SP-D, and indicative of insulin resistance. However, restricted diets eliminated all metabolic differences except the distribution of body fat. SP-D deficiency was further associated with elevated levels of systemic bacterial lipopolysaccharide.In conclusion, our findings suggest that lack of SP-D mediates modulation of food intake not directly involving hypothalamic regulatory pathways. The resulting accumulation of adipose tissue was associated with insulin resistance. The data suggest SP-D as a regulator of energy intake and body composition and an inhibitor of metabolic endotoxemia. SP-D may play a causal role at the crossroads of inflammation, obesity, and insulin resistance.
authors.affiliation: Cardiovascular and Renal Research, Institute for Molecular Medicine, University of Southern Denmark, Odense, Denmark.
authors.forename: Jacob V
authors.initials: JV
authors.lastname: Stidsen
authors.forename: Reza
authors.initials: R
authors.lastname: Khorooshi
authors.forename: Martin K U
authors.initials: MK
authors.lastname: Rahbek
authors.forename: Katrine L
authors.initials: KL
authors.lastname: Kirketerp-Møller
authors.forename: Pernille B L
authors.initials: PB
authors.lastname: Hansen
authors.forename: Peter
authors.initials: P
authors.lastname: Bie
authors.forename: Karin
authors.initials: K
authors.lastname: Kejling
authors.forename: Susanne
authors.initials: S
authors.lastname: Mandrup
authors.forename: Samuel
authors.initials: S
authors.lastname: Hawgood
authors.forename: Ole
authors.initials: O
authors.lastname: Nielsen
authors.forename: Claus H
authors.initials: CH
authors.lastname: Nielsen
authors.forename: Trevor
authors.initials: T
authors.lastname: Owens
authors.forename: Uffe
authors.initials: U
authors.lastname: Holmskov
authors.forename: Grith L
authors.initials: GL
authors.lastname: Sørensen
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose; D002490:Central Nervous System / Q000187:drug effects; D019446:Endotoxemia / Q000235:genetics; D004734:Energy Metabolism / Q000235:genetics*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D006963:Hyperphagia / Q000235:genetics / Q000378:metabolism; D007113:Immunity, Innate / Q000187:drug effects; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000235:genetics; D020738:Leptin / Q000097:blood; D008168:Lung / Q000378:metabolism*; D051379:Mice; D037663:Pulmonary Surfactant-Associated Protein D / Q000008:administration & dosage / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*
chemical_list: D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D020738:Leptin; D037663:Pulmonary Surfactant-Associated Protein D