Next Article in Journal
Lipidomics of Brain Tissues in Rats Fed Human Milk from Chinese Mothers or Commercial Infant Formula
Next Article in Special Issue
Exposure of HepaRG Cells to Sodium Saccharin Underpins the Importance of Including Non-Hepatotoxic Compounds When Investigating Toxicological Modes of Action Using Metabolomics
Previous Article in Journal
Creating a Reliable Mass Spectral–Retention Time Library for All Ion Fragmentation-Based Metabolomics
Previous Article in Special Issue
Hepatic Metabolic Derangements Triggered by Hyperthermia: An In Vitro Metabolomic Study
Open AccessArticle

A Lipidomic Analysis of Docosahexaenoic Acid (22:6, ω3) Mediated Attenuation of Western Diet Induced Nonalcoholic Steatohepatitis in Male Ldlr -/- Mice

1
Nutrition Program, School of Biological and Population Health Sciences, Oregon State University, Corvallis, OR 97331, USA
2
Department of Chemistry, Oregon State University, Corvallis, OR 97331, USA
3
The Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA
*
Author to whom correspondence should be addressed.
Current affiliation: Endocrine Research Unit, Mayo Clinic, Rochester, MN 55902, USA.
Metabolites 2019, 9(11), 252; https://doi.org/10.3390/metabo9110252
Received: 21 September 2019 / Revised: 14 October 2019 / Accepted: 22 October 2019 / Published: 28 October 2019
(This article belongs to the Special Issue Metabolism and Metabolomics of Liver in Health and Disease)
Nonalcoholic fatty liver disease (NAFLD) is a major public health problem worldwide. NAFLD ranges in severity from benign steatosis to nonalcoholic steatohepatitis (NASH), cirrhosis, and primary hepatocellular cancer (HCC). Obesity and type 2 diabetes mellitus (T2DM) are strongly associated with NAFLD, and the western diet (WD) is a major contributor to the onset and progression of these chronic diseases. Our aim was to use a lipidomic approach to identify potential lipid mediators of diet-induced NASH. We previously used a preclinical mouse (low density lipoprotein receptor null mouse, Ldlr -/-) model to assess transcriptomic mechanisms linked to WD-induced NASH and docosahexaenoic acid (DHA, 22:6, ω3)-mediated remission of NASH. This report used livers from the previous study to carry out ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) and high-performance liquid chromatography coupled with dynamic multi-reaction monitoring (HPLC-dMRM) to assess the impact of the WD and DHA on hepatic membrane lipid and oxylipin composition, respectively. Feeding mice the WD increased hepatic saturated and monounsaturated fatty acids and arachidonic acid (ARA, 20:4, ω6) in membrane lipids and suppressed ω3 polyunsaturated fatty acids (PUFA) in membrane lipids and ω3 PUFA-derived anti-inflammatory oxylipins. Supplementing the WD with DHA lowered hepatic ARA in membrane lipids and ARA-derived oxylipins and significantly increased hepatic DHA and its metabolites in membrane lipids, as well as C20–22 ω3 PUFA-derived oxylipins. NASH markers of inflammation and fibrosis were inversely associated with hepatic C20–22 ω3 PUFA-derived Cyp2C- and Cyp2J-generated anti-inflammatory oxylipins (false discovery rate adjusted p-value; q ≤ 0.026). Our findings suggest that dietary DHA promoted partial remission of WD-induced NASH, at least in part, by lowering hepatic pro-inflammatory oxylipins derived from ARA and increasing hepatic anti-inflammatory oxylipins derived from C20–22 ω3 PUFA. View Full-Text
Keywords: nonalcoholic fatty liver disease; nonalcoholic steatohepatitis; arachidonic acid; docosahexaenoic acid; inflammation; fibrosis; lipidomics; mass spectrometry nonalcoholic fatty liver disease; nonalcoholic steatohepatitis; arachidonic acid; docosahexaenoic acid; inflammation; fibrosis; lipidomics; mass spectrometry
Show Figures

Graphical abstract

MDPI and ACS Style

García-Jaramillo, M.; Lytle, K.A.; Spooner, M.H.; Jump, D.B. A Lipidomic Analysis of Docosahexaenoic Acid (22:6, ω3) Mediated Attenuation of Western Diet Induced Nonalcoholic Steatohepatitis in Male Ldlr -/- Mice. Metabolites 2019, 9, 252.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop