Influence of gender, obesity, and muscle lipase activity on intramyocellular lipids in sedentary individuals.
BACKGROUND
Obesity and type 2 diabetes are associated with elevated intramyocellular lipids (IMCLs) and insulin resistance.


OBJECTIVE
We tested the hypothesis that skeletal muscle lipases activity could influence IMCL content (including diacylglycerol and ceramides).


METHODS
The present study included 48 subjects with a wide range of age (19-68 yr) and body mass index (20-45 kg/m(2)) who underwent skeletal muscle biopsy, dual-energy x-ray absorptiometry and a hyperinsulinemic euglycemic clamp.


METHODS
Insulin sensitivity by hyperinsulinemic clamp, and intramyocellular triacylglycerol (IMTG), diacylglycerol (DAG), and ceramides content, and triacylglycerol and diacylglycerol hydrolase activities were measured in biopsies of vastus lateralis. IMCL was measured by (1)H-magnetic resonance spectroscopy in a subgroup of 25 subjects. Multivariate regression analyses were performed to identify the main predictors of IMCL.


RESULTS
Body fat was the main predictor of IMTG independently of the method and the type of muscle; IMTG concentration was higher in females vs. males and obese vs. nonobese subjects. Muscle DAG and ceramides concentrations were elevated in obese and type 2 diabetic subjects and were not related to body fat and fasting free fatty acids, whereas a direct association with the ratio of diacylglycerol hydrolase to triacylglycerol hydrolase activity (an index of incomplete triacylglycerol hydrolysis) was observed, which explained 54 and 38% of the variance in DAG and ceramides (P < 0.001), respectively. DAG content was the main determinant of insulin resistance.


CONCLUSIONS
These data suggest that intramyocellular DAG is an independent predictor of insulin resistance in humans and that its levels correlate with lipolytic enzymes activity in skeletal muscle but not with markers of adiposity.
Moro
Cedric
C
Department of Molecular and Experimental Endocrinology, Pennington Biomedical Research Center, 6400 Perkins Road, Baton Rouge, Louisiana 70808, USA. cedric.moro@pbrc.edu
Galgani
Jose E
JE
Luu
LanChi
L
Pasarica
Magdalena
M
Mairal
Aline
A
Bajpeyi
Sudip
S
Schmitz
Gerd
G
Langin
Dominique
D
Liebisch
Gerhard
G
Smith
Steven R
SR
D000328:Adult; D000368:Aged; D002518:Ceramides / Q000378:metabolism; D004075:Diglycerides / Q000378:metabolism*; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D008049:Lipase / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism*; D012737:Sex Factors; D014280:Triglycerides / Q000378:metabolism
D002518:Ceramides; D004075:Diglycerides; D014280:Triglycerides; D008049:Lipase