Reduced CD300LG mRNA tissue expression, increased intramyocellular lipid content and impaired glucose metabolism in healthy male carriers of Arg82Cys in CD300LG: a novel genometabolic cross-link between CD300LG and common metabolic phenotypes

Julie Støy; Ulla Kampmann; Annette Mengel; Nils E Magnusson; Niels Jessen; Niels Grarup; Jørgen Rungby; Hans Stødkilde-Jørgensen; Ivan Brandslund; Cramer Christensen; Torben Hansen; Oluf Pedersen; Niels Møller

doi:10.1136/bmjdrc-2015-000095

Reduced CD300LG mRNA tissue expression, increased intramyocellular lipid content and impaired glucose metabolism in healthy male carriers of Arg82Cys in CD300LG: a novel genometabolic cross-link between CD300LG and common metabolic phenotypes

Julie Støy, Ulla Kampmann, Annette Mengel, Nils E Magnusson, Niels Jessen, Niels Grarup, Jørgen Rungby, Hans Stødkilde-Jørgensen, Ivan Brandslund, Cramer Christensen, Torben Hansen, Oluf Pedersen, Niels Møller

Department of Clinical Medicine

5 Citations (Scopus)

Abstract

Background: CD300LG rs72836561 (c.313C>T, p. Arg82Cys) has in genetic-epidemiological studies been associated with the lipoprotein abnormalities of the metabolic syndrome. CD300LG belongs to the CD300- family of membrane-bound molecules which have the ability to recognize and interact with extracellular lipids. We tested whether this specific polymorphism results in abnormal lipid accumulation in skeletal muscle and liver and other indices of metabolic dysfunction. Methods: 40 healthy men with a mean age of 55 years were characterized metabolically including assessment of insulin sensitivity by the hyperinsulinemic euglycemic clamp, intrahepatic lipid content (IHLC) and intramyocellular lipid content (IMCL) by MR spectroscopy, and β-cell function by an intravenous glucose tolerance test. Changes in insulin signaling and CD300LG mRNA expression were determined by western blotting and quantitative PCR in muscle and adipose tissue. Results: Compared with the 20 controls (CC carriers), the 20 CT carriers (polymorphism carriers) had higher IMCL (p=0.045), a reduced fasting forearm glucose uptake (p=0.011), a trend toward lower M-values during the clamp; 6.0 mg/kg/min vs 7.1 (p=0.10), and higher IHLC (p=0.10). CT carriers had lower CD300LG mRNA expression and CD300LG expression in muscle correlated with IMCL (β=−0.35, p=0.046), forearm glucose uptake (β=0.37, p=0.03), and tended to correlate with the M-value (β=0.33, p=0.06), independently of CD300LG genotype. β-cell function was unaffected. Conclusions: The CD300LG polymorphism was associated with decreased CD300LG mRNA expression in muscle and adipose tissue, increased IMCL, and abnormalities of glucose metabolism. CD300LG mRNA levels correlated with IMCL and forearm glucose uptake. These findings link a specific CD300LG polymorphism with features of the metabolic syndrome suggesting a role for CD300LG in the regulation of common metabolic traits.

Original language	English
Article number	e000095
Journal	BMJ open diabetes research & care
Volume	3
Issue number	1
Pages (from-to)	1-12
Number of pages	12
ISSN	2052-4897
DOIs	https://doi.org/10.1136/bmjdrc-2015-000095
Publication status	Published - 26 Aug 2015

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Støy, J., Kampmann, U., Mengel, A., Magnusson, N. E., Jessen, N., Grarup, N., Rungby, J., Stødkilde-Jørgensen, H., Brandslund, I., Christensen, C., Hansen, T., Pedersen, O., & Møller, N. (2015). Reduced CD300LG mRNA tissue expression, increased intramyocellular lipid content and impaired glucose metabolism in healthy male carriers of Arg82Cys in CD300LG: a novel genometabolic cross-link between CD300LG and common metabolic phenotypes. BMJ open diabetes research & care, 3(1), 1-12. Article e000095. https://doi.org/10.1136/bmjdrc-2015-000095

Reduced CD300LG mRNA tissue expression, increased intramyocellular lipid content and impaired glucose metabolism in healthy male carriers of Arg82Cys in CD300LG: a novel genometabolic cross-link between CD300LG and common metabolic phenotypes. / Støy, Julie; Kampmann, Ulla; Mengel, Annette et al.
In: BMJ open diabetes research & care, Vol. 3, No. 1, e000095, 26.08.2015, p. 1-12.

Research output: Contribution to journal › Journal article › Research › peer-review

Støy, J, Kampmann, U, Mengel, A, Magnusson, NE, Jessen, N, Grarup, N , Rungby, J, Stødkilde-Jørgensen, H, Brandslund, I, Christensen, C, Hansen, T , Pedersen, O & Møller, N 2015, 'Reduced CD300LG mRNA tissue expression, increased intramyocellular lipid content and impaired glucose metabolism in healthy male carriers of Arg82Cys in CD300LG: a novel genometabolic cross-link between CD300LG and common metabolic phenotypes', BMJ open diabetes research & care, vol. 3, no. 1, e000095, pp. 1-12. https://doi.org/10.1136/bmjdrc-2015-000095

Støy J, Kampmann U, Mengel A, Magnusson NE, Jessen N, Grarup N et al. Reduced CD300LG mRNA tissue expression, increased intramyocellular lipid content and impaired glucose metabolism in healthy male carriers of Arg82Cys in CD300LG: a novel genometabolic cross-link between CD300LG and common metabolic phenotypes. BMJ open diabetes research & care. 2015 Aug 26;3(1):1-12. e000095. doi: 10.1136/bmjdrc-2015-000095

Støy, Julie ; Kampmann, Ulla ; Mengel, Annette et al. / Reduced CD300LG mRNA tissue expression, increased intramyocellular lipid content and impaired glucose metabolism in healthy male carriers of Arg82Cys in CD300LG : a novel genometabolic cross-link between CD300LG and common metabolic phenotypes. In: BMJ open diabetes research & care. 2015 ; Vol. 3, No. 1. pp. 1-12.

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title = "Reduced CD300LG mRNA tissue expression, increased intramyocellular lipid content and impaired glucose metabolism in healthy male carriers of Arg82Cys in CD300LG: a novel genometabolic cross-link between CD300LG and common metabolic phenotypes",

abstract = "Background: CD300LG rs72836561 (c.313C>T, p. Arg82Cys) has in genetic-epidemiological studies been associated with the lipoprotein abnormalities of the metabolic syndrome. CD300LG belongs to the CD300- family of membrane-bound molecules which have the ability to recognize and interact with extracellular lipids. We tested whether this specific polymorphism results in abnormal lipid accumulation in skeletal muscle and liver and other indices of metabolic dysfunction. Methods: 40 healthy men with a mean age of 55 years were characterized metabolically including assessment of insulin sensitivity by the hyperinsulinemic euglycemic clamp, intrahepatic lipid content (IHLC) and intramyocellular lipid content (IMCL) by MR spectroscopy, and β-cell function by an intravenous glucose tolerance test. Changes in insulin signaling and CD300LG mRNA expression were determined by western blotting and quantitative PCR in muscle and adipose tissue. Results: Compared with the 20 controls (CC carriers), the 20 CT carriers (polymorphism carriers) had higher IMCL (p=0.045), a reduced fasting forearm glucose uptake (p=0.011), a trend toward lower M-values during the clamp; 6.0 mg/kg/min vs 7.1 (p=0.10), and higher IHLC (p=0.10). CT carriers had lower CD300LG mRNA expression and CD300LG expression in muscle correlated with IMCL (β=−0.35, p=0.046), forearm glucose uptake (β=0.37, p=0.03), and tended to correlate with the M-value (β=0.33, p=0.06), independently of CD300LG genotype. β-cell function was unaffected. Conclusions: The CD300LG polymorphism was associated with decreased CD300LG mRNA expression in muscle and adipose tissue, increased IMCL, and abnormalities of glucose metabolism. CD300LG mRNA levels correlated with IMCL and forearm glucose uptake. These findings link a specific CD300LG polymorphism with features of the metabolic syndrome suggesting a role for CD300LG in the regulation of common metabolic traits.",

author = "Julie St{\o}y and Ulla Kampmann and Annette Mengel and Magnusson, {Nils E} and Niels Jessen and Niels Grarup and J{\o}rgen Rungby and Hans St{\o}dkilde-J{\o}rgensen and Ivan Brandslund and Cramer Christensen and Torben Hansen and Oluf Pedersen and Niels M{\o}ller",

year = "2015",

month = aug,

day = "26",

doi = "10.1136/bmjdrc-2015-000095",

language = "English",

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pages = "1--12",

journal = "BMJ open diabetes research & care",

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TY - JOUR

T1 - Reduced CD300LG mRNA tissue expression, increased intramyocellular lipid content and impaired glucose metabolism in healthy male carriers of Arg82Cys in CD300LG

T2 - a novel genometabolic cross-link between CD300LG and common metabolic phenotypes

AU - Støy, Julie

AU - Kampmann, Ulla

AU - Mengel, Annette

AU - Magnusson, Nils E

AU - Jessen, Niels

AU - Grarup, Niels

AU - Rungby, Jørgen

AU - Stødkilde-Jørgensen, Hans

AU - Brandslund, Ivan

AU - Christensen, Cramer

AU - Hansen, Torben

AU - Pedersen, Oluf

AU - Møller, Niels

PY - 2015/8/26

Y1 - 2015/8/26

N2 - Background: CD300LG rs72836561 (c.313C>T, p. Arg82Cys) has in genetic-epidemiological studies been associated with the lipoprotein abnormalities of the metabolic syndrome. CD300LG belongs to the CD300- family of membrane-bound molecules which have the ability to recognize and interact with extracellular lipids. We tested whether this specific polymorphism results in abnormal lipid accumulation in skeletal muscle and liver and other indices of metabolic dysfunction. Methods: 40 healthy men with a mean age of 55 years were characterized metabolically including assessment of insulin sensitivity by the hyperinsulinemic euglycemic clamp, intrahepatic lipid content (IHLC) and intramyocellular lipid content (IMCL) by MR spectroscopy, and β-cell function by an intravenous glucose tolerance test. Changes in insulin signaling and CD300LG mRNA expression were determined by western blotting and quantitative PCR in muscle and adipose tissue. Results: Compared with the 20 controls (CC carriers), the 20 CT carriers (polymorphism carriers) had higher IMCL (p=0.045), a reduced fasting forearm glucose uptake (p=0.011), a trend toward lower M-values during the clamp; 6.0 mg/kg/min vs 7.1 (p=0.10), and higher IHLC (p=0.10). CT carriers had lower CD300LG mRNA expression and CD300LG expression in muscle correlated with IMCL (β=−0.35, p=0.046), forearm glucose uptake (β=0.37, p=0.03), and tended to correlate with the M-value (β=0.33, p=0.06), independently of CD300LG genotype. β-cell function was unaffected. Conclusions: The CD300LG polymorphism was associated with decreased CD300LG mRNA expression in muscle and adipose tissue, increased IMCL, and abnormalities of glucose metabolism. CD300LG mRNA levels correlated with IMCL and forearm glucose uptake. These findings link a specific CD300LG polymorphism with features of the metabolic syndrome suggesting a role for CD300LG in the regulation of common metabolic traits.

AB - Background: CD300LG rs72836561 (c.313C>T, p. Arg82Cys) has in genetic-epidemiological studies been associated with the lipoprotein abnormalities of the metabolic syndrome. CD300LG belongs to the CD300- family of membrane-bound molecules which have the ability to recognize and interact with extracellular lipids. We tested whether this specific polymorphism results in abnormal lipid accumulation in skeletal muscle and liver and other indices of metabolic dysfunction. Methods: 40 healthy men with a mean age of 55 years were characterized metabolically including assessment of insulin sensitivity by the hyperinsulinemic euglycemic clamp, intrahepatic lipid content (IHLC) and intramyocellular lipid content (IMCL) by MR spectroscopy, and β-cell function by an intravenous glucose tolerance test. Changes in insulin signaling and CD300LG mRNA expression were determined by western blotting and quantitative PCR in muscle and adipose tissue. Results: Compared with the 20 controls (CC carriers), the 20 CT carriers (polymorphism carriers) had higher IMCL (p=0.045), a reduced fasting forearm glucose uptake (p=0.011), a trend toward lower M-values during the clamp; 6.0 mg/kg/min vs 7.1 (p=0.10), and higher IHLC (p=0.10). CT carriers had lower CD300LG mRNA expression and CD300LG expression in muscle correlated with IMCL (β=−0.35, p=0.046), forearm glucose uptake (β=0.37, p=0.03), and tended to correlate with the M-value (β=0.33, p=0.06), independently of CD300LG genotype. β-cell function was unaffected. Conclusions: The CD300LG polymorphism was associated with decreased CD300LG mRNA expression in muscle and adipose tissue, increased IMCL, and abnormalities of glucose metabolism. CD300LG mRNA levels correlated with IMCL and forearm glucose uptake. These findings link a specific CD300LG polymorphism with features of the metabolic syndrome suggesting a role for CD300LG in the regulation of common metabolic traits.

U2 - 10.1136/bmjdrc-2015-000095

DO - 10.1136/bmjdrc-2015-000095

M3 - Journal article

C2 - 26336608

SN - 2052-4897

VL - 3

SP - 1

EP - 12

JO - BMJ open diabetes research & care

JF - BMJ open diabetes research & care

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