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.
Smith
Brennan K
BK
Department of Human Health and Nutritional Sciences, College of Biological Science, University of Guelph, Guelph, ON N1G 2W1, Canada.
Holloway
Graham P
GP
Reza-Lopez
Sandra
S
Jeram
Stanley M
SM
Kang
Jing X
JX
Ma
David W L
DW
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