Surfactant protein d deficiency in mice is associated with hyperphagia, altered fat deposition, insulin resistance, and increased Basal endotoxemia

Jacob V Stidsen, Reza Khorooshi, Martin K U Rahbek, Katrine Lindequist Kirketerp-Møller, Pernille B L Hansen, Peter Bie, Karin Kejling, Susanne Mandrup, Samuel Hawgood, Ole Stig Nielsen, Claus Nielsen, Trevor Owens, Uffe Holmskov, Grith L Sørensen

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

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.
OriginalsprogEngelsk
TidsskriftP L o S One
Vol/bind7
Udgave nummer4
Sider (fra-til)e35066
ISSN1932-6203
DOI
StatusUdgivet - 2012

Fingeraftryk

Pulmonary Surfactant-Associated Protein D
Protein Deficiency
overeating
endotoxemia
Endotoxemia
insulin resistance
Surface-Active Agents
surfactants
Insulin Resistance
Fats
Insulin
mice
lipids
Proteins
proteins
energy intake
Energy Metabolism
inflammation
pro-opiomelanocortin
Tissue

Citer dette

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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.",
author = "Stidsen, {Jacob V} and Reza Khorooshi and Rahbek, {Martin K U} and Kirketerp-M{\o}ller, {Katrine Lindequist} and Hansen, {Pernille B L} and Peter Bie and Karin Kejling and Susanne Mandrup and Samuel Hawgood and Nielsen, {Ole Stig} and Claus Nielsen and Trevor Owens and Uffe Holmskov and S{\o}rensen, {Grith L}",
year = "2012",
doi = "10.1371/journal.pone.0035066",
language = "English",
volume = "7",
pages = "e35066",
journal = "P L o S One",
issn = "1932-6203",
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Surfactant protein d deficiency in mice is associated with hyperphagia, altered fat deposition, insulin resistance, and increased Basal endotoxemia. / Stidsen, Jacob V; Khorooshi, Reza; Rahbek, Martin K U; Kirketerp-Møller, Katrine Lindequist; Hansen, Pernille B L; Bie, Peter; Kejling, Karin; Mandrup, Susanne; Hawgood, Samuel; Nielsen, Ole Stig; Nielsen, Claus; Owens, Trevor; Holmskov, Uffe; Sørensen, Grith L.

I: P L o S One, Bind 7, Nr. 4, 2012, s. e35066.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Surfactant protein d deficiency in mice is associated with hyperphagia, altered fat deposition, insulin resistance, and increased Basal endotoxemia

AU - Stidsen, Jacob V

AU - Khorooshi, Reza

AU - Rahbek, Martin K U

AU - Kirketerp-Møller, Katrine Lindequist

AU - Hansen, Pernille B L

AU - Bie, Peter

AU - Kejling, Karin

AU - Mandrup, Susanne

AU - Hawgood, Samuel

AU - Nielsen, Ole Stig

AU - Nielsen, Claus

AU - Owens, Trevor

AU - Holmskov, Uffe

AU - Sørensen, Grith L

PY - 2012

Y1 - 2012

N2 - 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.

AB - 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.

U2 - 10.1371/journal.pone.0035066

DO - 10.1371/journal.pone.0035066

M3 - Journal article

C2 - 22509382

VL - 7

SP - e35066

JO - P L o S One

JF - P L o S One

SN - 1932-6203

IS - 4

ER -