Data from: Dietary macronutrients modulate the fatty acyl composition of rat liver mitochondrial cardiolipins

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 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.本研究以雄性FBNF1大鼠为实验对象，喂食20种不同的低脂等热量日粮，探究膳食脂肪与碳水化合物对肝脏线粒体的交互作用。动物生长速率与线粒体呼吸参数基本未受影响，但基于质谱的线粒体脂质组学分析显示，喂食高血糖指数的饱和脂肪或反式脂肪日粮的大鼠，其心磷脂（cardiolipins, CLs）水平显著升高——心磷脂是一类对线粒体结构与功能至关重要的磷脂家族。此类线粒体还表现出单溶血心磷脂（monolysocardiolipins，心磷脂的前体/降解产物）水平升高，反式磷脂酰胆碱(18:1/18:1) [trans PC (18:1/18:1)] 与顺式磷脂酰胆碱(18:1/18:1) [cis PC (18:1/18:1)] 的比值升高（该指标可作为硫自由基应激的标志物），以及泛醌Q9水平降低；后两项结果提示存在轻度线粒体氧化还原异常。进一步分析表明：(i) 膳食脂肪以及（程度相对较弱的）碳水化合物会诱导特定心磷脂物种的相对丰度发生改变；(ii) 脂肪酸（Fatty acid, FA）掺入成熟心磷脂的过程同时受到正向（>400倍）与负向（2.5倍）调控；(iii) 膳食脂质丰度与脂肪酸掺入心磷脂库及特定成熟四酰基心磷脂的过程呈负相关，这提示了此前未被发现的代偿调控机制。本研究揭示了线粒体代谢核心脂质此前未被认知的复杂性与调控规律。