Abstract
The interaction of dietary fats and carbohydrates on liver mitochondria were examined in male FBNF1 rats fed 20 different low-fat isocaloric diets. Animal growth rates and mitochondrial respiratory parameters were essentially unaffected, but mass spectrometry-based mitochondrial lipidomics profiling revealed increased levels of cardiolipins (CLs), a family of phospholipids essential for mitochondrial structure and function, in rats fed saturated or trans fat-based diets with a high glycemic index. These mitochondria showed elevated monolysocardiolipins (a CL precursor/product of CL degradation), elevated ratio of trans-phosphocholine (PC) (18:1/18:1) to cis-PC (18:1/18:1) (a marker of thiyl radical stress), and decreased ubiquinone Q9; the latter two of which imply a low-grade mitochondrial redox abnormality. Extended analysis demonstrated: i) dietary fats and, to a lesser extent, carbohydrates induce changes in the relative abundance of specific CL species; ii) fatty acid (FA) incorporation into mature CLs undergoes both positive (>400-fold) and negative (2.5-fold) regulation; and iii) dietary lipid abundance and incorporation of FAs into both the CL pool and specific mature tetra-acyl CLs are inversely related, suggesting previously unobserved compensatory regulation. This study reveals previously unobserved complexity/regulation of the central lipid in mitochondrial metabolism.
Highlights
The interaction of dietary fats and carbohydrates on liver mitochondria were examined in male Fisher × Brown Norway F1 (FBNF1) rats fed 20 different low-fat isocaloric diets
There were no significant differences in food consumption or body weight gain across all diets, rats on trans fatty acid (TFA) diets, regardless of carbohydrate source, exhibited a trend of having the highest body weight at the time of sacrifice
In contrast to the working hypothesis, the mean total CL levels were increased ف50% by high GI (HGI) diets containing TFA or saturated fatty acid (SFA) relative to the level associated with other diets (Fig. 1A, P < 10Ϫ15 by ANOVA, supplementary Fig. IA for these data broken down by fat)
Summary
The interaction of dietary fats and carbohydrates on liver mitochondria were examined in male FBNF1 rats fed 20 different low-fat isocaloric diets. In contrast to the working hypothesis, the mean total CL levels were increased ف50% by HGI diets containing TFA or SFA relative to the level associated with other diets (Fig. 1A, P < 10Ϫ15 by ANOVA, supplementary Fig. IA for these data broken down by fat).
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