Department of Pharmacology, School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia.
Diabetes & Metabolism Division, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.
Sci Rep. 2017 Oct 24;7(1):13914. doi: 10.1038/s41598-017-14214-1.
Different mouse strains exhibit variation in their inherent propensities to develop metabolic disease. We recently showed that C57BL6, 129X1, DBA/2 and FVB/N mice are all susceptible to high-fat diet-induced glucose intolerance, while BALB/c mice are relatively protected, despite changes in many factors linked with insulin resistance. One parameter strongly linked with insulin resistance is ectopic lipid accumulation, especially metabolically active ceramides and diacylglycerols (DAG). This study examined diet-induced changes in the skeletal muscle lipidome across these five mouse strains. High-fat feeding increased total muscle triacylglycerol (TAG) content, with elevations in similar triacylglycerol species observed for all strains. There were also generally consistent changes across strains in the abundance of different phospholipid (PL) classes and the fatty acid profile of phospholipid molecular species, with the exception being a strain-specific difference in phospholipid species containing two polyunsaturated fatty acyl chains in BALB/c mice (i.e. a diet-induced decrease in the other four strains, but no change in BALB/c mice). In contrast to TAG and PL, the high-fat diet had a minor influence on DAG and ceramide species across all strains. These results suggest that widespread alterations in muscle lipids are unlikely a major contributors to the favourable metabolic profile of BALB/c mice and rather there is a relatively conserved high-fat diet response in muscle of most mouse strains.
不同的小鼠品系在其内在发展代谢疾病的倾向方面存在差异。我们最近表明，C57BL6、129X1、DBA/2 和 FVB/N 小鼠均易发生高脂肪饮食诱导的葡萄糖不耐受，而 BALB/c 小鼠则相对受到保护，尽管与胰岛素抵抗相关的许多因素发生了变化。与胰岛素抵抗密切相关的一个参数是异位脂质积累，特别是代谢活跃的神经酰胺和二酰基甘油（DAG）。本研究检测了这五种小鼠品系中高脂肪饮食引起的骨骼肌脂质组的变化。高脂肪喂养增加了肌肉总三酰甘油（TAG）含量，所有品系的类似三酰甘油种类都有升高。不同磷脂（PL）类别的丰度和磷脂分子种类的脂肪酸谱在不同品系之间也存在普遍一致的变化，除了 BALB/c 小鼠中含有两个多不饱和脂肪酸酰基链的磷脂种类存在品系特异性差异（即其他四个品系的饮食诱导减少，但 BALB/c 小鼠没有变化）。与 TAG 和 PL 不同，高脂肪饮食对所有品系的 DAG 和神经酰胺种类的影响较小。这些结果表明，肌肉脂质的广泛改变不太可能是 BALB/c 小鼠良好代谢特征的主要原因，而是大多数小鼠品系的肌肉对高脂肪饮食的反应相对保守。
