title: Dietary macronutrients modulate the fatty acyl composition of rat liver mitochondrial cardiolipins.
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.
authors.affiliation: Department of Neurosurgery, Brigham and Women's Hospital, Department of Surgery, Harvard Medical School, Boston, MA 02115.
authors.forename: Irina G
authors.initials: IG
authors.lastname: Stavrovskaya
authors.forename: Susan S
authors.initials: SS
authors.lastname: Bird
authors.forename: Vasant R
authors.initials: VR
authors.lastname: Marur
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Sniatynski
authors.forename: Sergei V
authors.initials: SV
authors.lastname: Baranov
authors.forename: Heather K
authors.initials: HK
authors.lastname: Greenberg
authors.forename: Caryn L
authors.initials: CL
authors.lastname: Porter
authors.forename: Bruce S
authors.initials: BS
authors.lastname: Kristal
mesh_terms: D000818:Animals; D002308:Cardiolipins / Q000378:metabolism*; D019069:Cell Respiration; D004032:Diet; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage / Q000378:metabolism*; D043371:Fatty Acids, Omega-6 / Q000008:administration & dosage / Q000378:metabolism*; D038321:Glycemic Index; D008099:Liver / Q000378:metabolism; D008297:Male; D008930:Mitochondria, Liver / Q000378:metabolism*; D018384:Oxidative Stress; D010101:Oxygen Consumption; D051381:Rats; D014451:Ubiquinone / Q000378:metabolism
chemical_list: D002308:Cardiolipins; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D014451:Ubiquinone; C030571:ubiquinone 9
keywords: glycemic index; lipidomics; mitochondria; monounsaturated fatty acids; polyunsaturated fatty acids; saturated fatty acids; trans fatty acids; ubiquinones