Chronic muscle stimulation improves insulin sensitivity while increasing subcellular lipid droplets and reducing selected diacylglycerol and ceramide species in obese Zucker rats.
OBJECTIVE
Although insulin resistance has been associated with accumulations of specific intramuscular fatty acids and altered subcellular localisation of lipid droplets, these concepts remain controversial. Therefore, we aimed to identify specific intramuscular fatty acids and subcellular lipid localisations associated with improved insulin sensitivity following chronic muscle contraction.


METHODS
In lean and insulin-resistant obese Zucker rats the tibialis anterior muscle was stimulated (6 h/day for 6 days). Thereafter, muscles were examined for insulin sensitivity, intramuscular lipid droplet localisation and triacylglycerol (TAG), diacylglycerol (DAG) and ceramide fatty acid composition.


RESULTS
In lean and obese animals, regardless of muscle type, chronic muscle contraction improved muscle insulin sensitivity and increased intramuscular levels of total and most C14-C22 TAG fatty acids (p < 0.05). Therefore, accumulation in subcellular lipid droplet compartments reflected the oversupply of lipids within muscle. In contrast, improvements in insulin sensitivity induced by muscle contraction were associated with reductions in specific DAG and ceramide species that were not uniform in red and white muscle of obese rats. However, these reductions were insufficient to fully normalise insulin sensitivity, indicating that other mechanisms are involved.


CONCLUSIONS
Reductions in 18 C length DAG and ceramide species were the most consistent in red and white muscle and therefore may represent therapeutic targets for improving insulin sensitivity.
Department of Human Health & Nutritional Sciences, University of Guelph, Guelph, ON, Canada, NIG, 2W1, ghollowa@uoguelph.ca.
Graham P
GP
Holloway
Xiao Xia
XX
Han
Swati S
SS
Jain
Arend
A
Bonen
Adrian
A
Chabowski
D000818:Animals; D002518:Ceramides / Q000378:metabolism*; D004075:Diglycerides / Q000378:metabolism*; D005260:Female; D007328:Insulin / Q000494:pharmacology*; D007333:Insulin Resistance; D009119:Muscle Contraction / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism*; D051381:Rats; D011924:Rats, Zucker; D014280:Triglycerides / Q000378:metabolism
C011439:1,2-diacylglycerol; D002518:Ceramides; D004075:Diglycerides; D007328:Insulin; D014280:Triglycerides