A decreased n-6/n-3 ratio in the fat-1 mouse is associated with improved glucose tolerance.

Abstract

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.

• Authors: Brennan K Smith, Graham P Holloway, Sandra Reza-Lopez, Stanley M Jeram, Jing X Kang, David W L Ma
• Journal: Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme (Appl Physiol Nutr Metab) Vol. 35 Issue 5 Pg. 699-706 (Oct 2010) ISSN: 1715-5312 [Print] Canada
• PMID: 20962926 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Blood Glucose
• Fatty Acids, Omega-3
• Fatty Acids, Omega-6
• Palmitates
• Phospholipids

Topics

• Animals
• Blood Glucose (metabolism)
• Fatty Acids, Omega-3 (metabolism)
• Fatty Acids, Omega-6 (metabolism)
• Female
• Glucose Intolerance (metabolism)
• Insulin Resistance (physiology)
• Male
• Mice
• Mice, Inbred C3H
• Mice, Inbred C57BL
• Mice, Transgenic
• Mitochondria (metabolism)
• Muscle, Skeletal (metabolism)
• Palmitates (metabolism)
• Phospholipids (metabolism)