A decreased n-6/n-3 ratio in the fat-1 mouse is associated with improved glucose tolerance.
A reduction in skeletal muscle fatty acid oxidation (FAO), manifested as a reduction in mitochondrial content and (or) FAO within mitochondria, may contribute to the development of insulin resistance. n-3 polyunsaturated fatty acids (PUFA) have been observed to increase the capacity for FAO and improve insulin sensitivity. We used the fat-1 mouse model, a transgenic animal capable of synthesizing n-3 PUFA from n-6 PUFA, to examine this relationship. Fat-1 mice exhibited a approximately 20-fold decrease in the n-6/n-3 ratio in skeletal muscle, and plasma glucose and the area under the glucose curve were significantly (p < 0.05) lower in fat-1 mice during a glucose challenge test. The improvement in whole-body glucose tolerance in the fat-1 mouse was associated with a approximately 21% (p < 0.05) decrease in whole-muscle citrate synthase (CS) activity (in red muscle only), without alterations in CS activity of isolated mitochondria (either red or white muscle; p > 0.05). These data suggest that the fat-1 mouse has decreased skeletal muscle mitochondrial content. However, the intrinsic ability of mitochondria to oxidize fatty acids was not altered in the fat-1 mouse, as rates of palmitate oxidation in isolated mitochondria from both red and white muscle were unchanged. Overall, this study demonstrates that a decrease in the n-6/n-3 ratio can enhance glucose tolerance in healthy animals, independent of changes in mitochondrial content.
Department of Human Health and Nutritional Sciences, College of Biological Science, University of Guelph, Guelph, ON N1G 2W1, Canada.
Brennan K
BK
Smith
Graham P
GP
Holloway
Sandra
S
Reza-Lopez
Stanley M
SM
Jeram
Jing X
JX
Kang
David W L
DW
Ma
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D015525:Fatty Acids, Omega-3 / Q000378:metabolism*; D043371:Fatty Acids, Omega-6 / Q000378:metabolism*; D005260:Female; D018149:Glucose Intolerance / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008928:Mitochondria / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism*; D010168:Palmitates / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism
D001786:Blood Glucose; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D010168:Palmitates; D010743:Phospholipids