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.
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.


BACKGROUND
NCT01571609.
Department of Internal Medicine and Endocrinology , Aarhus University Hospital , Aarhus , Denmark.
Julie
J
Støy
Department of Internal Medicine and Endocrinology , Aarhus University Hospital , Aarhus , Denmark.
Ulla
U
Kampmann
Medical Research Laboratories, Institute for Clinical Medicine, Aarhus University , Aarhus , Denmark.
Annette
A
Mengel
Medical Research Laboratories, Institute for Clinical Medicine, Aarhus University , Aarhus , Denmark.
Nils E
NE
Magnusson
Research Laboratory for Biochemical Pathology , Institute for Clinical Medicine, Aarhus University , Aarhus , Denmark.
Niels
N
Jessen
Faculty of Health and Medical Sciences , The Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen , Copenhagen , Denmark.
Niels
N
Grarup
Center for Diabetes Research and Department of Clinical Pharmacology, University Hospital of Copenhagen , Copenhagen , Denmark ; Department of Biomedicine , Aarhus University , Aarhus , Denmark.
Jørgen
J
Rungby
The MR Research Center, Aarhus University Hospital , Aarhus , Denmark.
Hans
H
Stødkilde-Jørgensen
Department of Clinical Biochemistry , Vejle Hospital , Vejle , Denmark.
Ivan
I
Brandslund
Department of Medicine , Vejle Hospital , Vejle , Denmark.
Cramer
C
Christensen
Faculty of Health and Medical Sciences , The Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen , Copenhagen , Denmark.
Torben
T
Hansen
Faculty of Health and Medical Sciences , The Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen , Copenhagen , Denmark.
Oluf
O
Pedersen
Department of Internal Medicine and Endocrinology , Aarhus University Hospital , Aarhus , Denmark ; Medical Research Laboratories, Institute for Clinical Medicine, Aarhus University , Aarhus , Denmark.
Niels
N
Møller
Gene Expression; Genetics; Insulin Resistance; Metabolic Syndrome