Yaligar Jadegoud, Gopalan Venkatesh, Kiat Ong Wee, Sugii Shigeki, Shui Guanghou, Lam Buu Duyen, Henry Christiani Jeyakumar, Wenk Markus R, Tai E Shyong, Velan S Sendhil
Laboratory of Molecular Imaging, Singapore Bioimaging Consortium, A*STAR, Singapore, Singapore.
Life Sciences Institute, National University of Singapore, Singapore, Singapore.
PLoS One. 2014 Mar 17;9(3):e91436. doi: 10.1371/journal.pone.0091436. eCollection 2014.
BACKGROUND & AIMS: Dietary saturated fatty acids contribute to the development of fatty liver and have pathogenic link to systemic inflammation. We investigated the effects of dietary fat towards the pathogenesis of non-alcoholic fatty liver disease by longitudinal in vivo magnetic resonance spectroscopy (MRS) and in vitro liquid chromatography coupled with mass spectrometry (LC-MS).
All measurements were performed on rats fed with high fat diet (HFD) and chow diet for twenty four weeks. Longitudinal MRS measurements were performed at the 12th, 18th and 24th weeks. Liver tissues were analyzed by LC-MS, histology and gene transcription studies after terminal in vivo experiments.
Liver fat content of HFD rats for all ages was significantly (P<0.05) higher compared to their respective chow diet fed rats. Unsaturation indices estimated from MRS and LC-MS data of chow diet fed rats were significantly higher (P<0.05) than HFD fed rats. The concentration of triglycerides 48∶1, 48∶2, 50∶1, 50∶2, 50∶3, 52∶1, 52∶2, 52∶3, 54∶3 and 54∶2 was significantly higher (P<0.05) in HFD rats. The concentration for some polyunsaturated triglycerides 54∶7, 56∶8, 56∶7, 58∶11, 58∶10, 58∶9, 58∶8 and 60∶10 was significantly higher (P<0.05) in chow diet fed rats compared to HFD rats. Lysophospholipid concentrations including LPC and LPE were higher in HFD rats at 24 weeks indicating the increased risk of diabetes. The expression of CD36, PPARα, SCD1, SREBF1 and UCP2 were significantly upregulated in HFD rats.
We demonstrated the early changes in saturated and unsaturated lipid composition in fatty liver by in vivo MRS and ex vivo LC-MS. The higher LPC concentration in HFD rats indicated a higher risk of developing diabetes. Early metabolic perturbations causing changes in lipid composition can be evaluated by the unsaturation index and correlated to the non alcoholic fatty liver disease.
膳食饱和脂肪酸会促使脂肪肝的发展，且与全身炎症存在致病关联。我们通过纵向体内磁共振波谱法（MRS）和体外液相色谱-质谱联用技术（LC-MS），研究了膳食脂肪对非酒精性脂肪性肝病发病机制的影响。
对喂食高脂饮食（HFD）和普通饮食24周的大鼠进行所有测量。在第12周、18周和24周进行纵向MRS测量。在体内实验结束后，通过LC-MS、组织学和基因转录研究对肝脏组织进行分析。
与各自喂食普通饮食的大鼠相比，所有年龄段的HFD大鼠肝脏脂肪含量均显著更高（P<0.05）。根据喂食普通饮食大鼠的MRS和LC-MS数据估算的不饱和度指数显著高于喂食HFD的大鼠（P<0.05）。HFD大鼠中甘油三酯48∶1、48∶2、50∶1、50∶2、50∶3、52∶1、52∶2、52∶3、54∶3和54∶2的浓度显著更高（P<0.05）。与HFD大鼠相比，喂食普通饮食的大鼠中一些多不饱和甘油三酯54∶7、56∶8、56∶7、58∶11、58∶10、58∶9、58∶8和60∶10的浓度显著更高（P<0.05）。24周时，HFD大鼠中溶血磷脂浓度（包括LPC和LPE）更高，表明糖尿病风险增加。HFD大鼠中CD36、PPARα、SCD1、SREBF1和UCP2的表达显著上调。
我们通过体内MRS和体外LC-MS证明了脂肪肝中饱和与不饱和脂质成分的早期变化。HFD大鼠中较高的LPC浓度表明患糖尿病的风险更高。可通过不饱和度指数评估导致脂质成分变化的早期代谢紊乱，并将其与非酒精性脂肪性肝病相关联。
