Evaluation of Dietary Effects on Hepatic Lipids in High Fat and Placebo Diet Fed Rats by in Vivo MRS and LC-MS Techniques

PLoS One. 2014 Mar 17;9(3):e91436. doi: 10.1371/journal.pone.0091436. eCollection 2014.

Abstract

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).

Methods: 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.

Results: 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.

Conclusions: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Glucose / metabolism
  • Body Weight
  • Chromatography, Liquid
  • Diet
  • Diet, High-Fat
  • Dietary Fats / metabolism*
  • Fatty Liver / metabolism
  • Fatty Liver / pathology
  • Gene Expression Profiling
  • Insulin / blood
  • Lipid Metabolism*
  • Lipids / blood
  • Lipids / chemistry
  • Liver / metabolism*
  • Magnetic Resonance Imaging
  • Magnetic Resonance Spectroscopy
  • Male
  • Mass Spectrometry
  • RNA, Messenger / genetics
  • Rats

Substances

  • Blood Glucose
  • Dietary Fats
  • Insulin
  • Lipids
  • RNA, Messenger

Grant support

This research was supported by the intramural funding from Singapore Bioimaging Consortium, A*STAR, Singapore & National University of Singapore, Singapore. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.