Display options
Cite
Støy J, Kampmann U, Mengel A, 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 Res Care. 2015;3(1):e000095doi: 10.1136/bmjdrc-2015-000095.
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), e000095. https://doi.org/10.1136/bmjdrc-2015-000095
Støy, Julie, 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 vol. 3,1 (2015): e000095. doi: https://doi.org/10.1136/bmjdrc-2015-000095
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. 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 Res Care. 2015 Aug 26;3(1):e000095. doi: 10.1136/bmjdrc-2015-000095. eCollection 2015. PMID: 26336608; PMCID: PMC4553907.
Copy Download .nbib Format: NLM
Share it on

BMJ Open Diabetes Res Care. 2015 Aug 26;3(1):e000095. doi: 10.1136/bmjdrc-2015-000095. eCollection 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

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

Affiliations

  1. Department of Internal Medicine and Endocrinology , Aarhus University Hospital , Aarhus , Denmark.
  2. Medical Research Laboratories, Institute for Clinical Medicine, Aarhus University , Aarhus , Denmark.
  3. Research Laboratory for Biochemical Pathology , Institute for Clinical Medicine, Aarhus University , Aarhus , Denmark.
  4. Faculty of Health and Medical Sciences , The Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen , Copenhagen , Denmark.
  5. Center for Diabetes Research and Department of Clinical Pharmacology, University Hospital of Copenhagen , Copenhagen , Denmark ; Department of Biomedicine , Aarhus University , Aarhus , Denmark.
  6. The MR Research Center, Aarhus University Hospital , Aarhus , Denmark.
  7. Department of Clinical Biochemistry , Vejle Hospital , Vejle , Denmark.
  8. Department of Medicine , Vejle Hospital , Vejle , Denmark.
  9. Department of Internal Medicine and Endocrinology , Aarhus University Hospital , Aarhus , Denmark ; Medical Research Laboratories, Institute for Clinical Medicine, Aarhus University , Aarhus , Denmark.

PMID: 26336608 PMCID: PMC4553907 DOI: 10.1136/bmjdrc-2015-000095

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.

TRIAL REGISTRATION NUMBER: NCT01571609.

Keywords: Gene Expression; Genetics; Insulin Resistance; Metabolic Syndrome

References

  1. Diabetes. 2001 Nov;50(11):2579-84 - PubMed
  2. Pediatrics. 2005 Mar;115(3):e290-6 - PubMed
  3. J Clin Invest. 1991 Jan;87(1):187-93 - PubMed
  4. Diabetes Care. 2001 Apr;24(4):683-9 - PubMed
  5. Endocr Rev. 1985 Winter;6(1):45-86 - PubMed
  6. Am J Physiol. 1978 Jan;234(1):E84-93 - PubMed
  7. Nat Methods. 2014 Feb;11(2):119-20 - PubMed
  8. Hypertension. 2000 Jul;36(1):7-13 - PubMed
  9. J Clin Invest. 1995 Dec;96(6):2802-8 - PubMed
  10. Diabetologia. 2011 Nov;54(11):2811-9 - PubMed
  11. Immunobiology. 2002 Sep;205(4-5):446-54 - PubMed
  12. Gastroenterology. 2008 May;134(5):1369-75 - PubMed
  13. Biochem Biophys Res Commun. 2006 Sep 15;348(1):183-91 - PubMed
  14. Immunogenetics. 2012 Jan;64(1):39-47 - PubMed
  15. Lancet. 2014 Mar 22;383(9922):1084-94 - PubMed
  16. J Am Coll Cardiol. 2010 Sep 28;56(14):1113-32 - PubMed
  17. Curr Mol Med. 2005 May;5(3):261-74 - PubMed
  18. Nature. 2010 Aug 5;466(7307):707-13 - PubMed
  19. Diabetes. 1999 Sep;48(9):1779-86 - PubMed
  20. Arch Intern Med. 2003 Feb 24;163(4):427-36 - PubMed
  21. J Clin Invest. 2004 Jun;113(11):1582-8 - PubMed
  22. PLoS Genet. 2013 Jun;9(6):e1003500 - PubMed
  23. Diabetologia. 2013 Feb;56(2):298-310 - PubMed
  24. Diabetes Care. 2003 May;26(5):1395-401 - PubMed
  25. Int J Epidemiol. 2013 Oct;42(5):1215-22 - PubMed
  26. Ann N Y Acad Sci. 1959 Sep 25;82:420-30 - PubMed
  27. J Clin Endocrinol Metab. 2009 Sep;94(9):3440-7 - PubMed
  28. Diabetologia. 2011 May;54(5):1147-56 - PubMed
  29. Blood. 2013 Mar 14;121(11):1951-60 - PubMed
  30. Am J Physiol. 1988 May;254(5 Pt 1):E562-5 - PubMed
  31. Diabetologia. 1989 Feb;32(2):105-10 - PubMed
  32. Nature. 1968 Jul 13;219(5150):193-5 - PubMed
  33. Int J Obes (Lond). 2008 Sep;32(9):1431-7 - PubMed
  34. Nat Genet. 2012 Sep;44(9):991-1005 - PubMed
  35. Crit Rev Immunol. 2011;31(2):147-69 - PubMed
  36. Am J Physiol. 1979 Sep;237(3):E214-23 - PubMed
  37. Am J Clin Nutr. 2012 Feb;95(2):283-9 - PubMed
  38. Magn Reson Med. 1993 Dec;30(6):672-9 - PubMed
  39. Nature. 2011 Sep 11;478(7367):103-9 - PubMed
  40. Recent Prog Horm Res. 1963;19:445-88 - PubMed
  41. PLoS One. 2014 Oct 14;9(10):e109646 - PubMed
  42. N Engl J Med. 2014 Sep 18;371(12):1131-41 - PubMed

Publication Types