Evidence map›Paper›PMID 24358308›Full record

ArticlePloS one2013

A metabolomic analysis of omega-3 fatty acid-mediated attenuation of western diet-induced nonalcoholic steatohepatitis in LDLR-/- mice.

Christopher M Depner, Maret G Traber, Gerd Bobe, Elizabeth Kensicki, Kurt M Bohren, Ginger Milne, Donald B Jump

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed, 1 pooled it
3.7field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

32 citing papers in PubMed, 1 synthesis or guideline pooled it, 59 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 4 institutions in 1 country.

Christopher M DepnerThe Nutrition Program, School of Biological and Population Health Sciences, Oregon State University, Corvallis, Oregon, United States of America ; The Linus Pauling Institute, Oregon State University, Corvallis, Oregon, United States of America.
Maret G TraberThe Nutrition Program, School of Biological and Population Health Sciences, Oregon State University, Corvallis, Oregon, United States of America ; The Linus Pauling Institute, Oregon State University, Corvallis, Oregon, United States of America.
Gerd BobeDepartment of Animal and Rangeland Sciences, Oregon State University, Corvallis, Oregon, United States of America ; The Linus Pauling Institute, Oregon State University, Corvallis, Oregon, United States of America.
Elizabeth KensickiMetabolon, Inc., Durham, North Carolina, United States of America.
Kurt M BohrenUnited States Department of Agriculture, Agricultural Research Service, Children's Nutrition Research Center, Baylor College of Medicine, Houston, Texas, United States of America.
Ginger MilneEicosanoid Core Laboratory, Division of Clinical Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America.
Donald B JumpThe Nutrition Program, School of Biological and Population Health Sciences, Oregon State University, Corvallis, Oregon, United States of America ; The Linus Pauling Institute, Oregon State University, Corvallis, Oregon, United States of America.
Oregon State University · USAgricultural Research Service · USMetabolon (United States) · USVanderbilt University Medical Center · US

Funding

DIETARY FAT REGULATION OF HEPATIC GENE EXPRESSIONR01DK043220 · NIDDK · OREGON STATE UNIVERSITY · PI JUMP, DONALD B · 1991 to 2009
$2.7M
PUFA Synthesis and the Control of Hepatic MetabolismR01DK094600 · NIDDK · OREGON STATE UNIVERSITY · PI JUMP, DONALD B · 2012 to 2015
$1.2M
NIDDK NIH HHS DK043220NIDDK NIH HHS DK094600NIDDK NIH HHS R01 DK043220NIDDK NIH HHS R01 DK094600
6 · The paper itself

Abstract

backgroundNonalcoholic steatohepatitis (NASH) is a progressive form of nonalcoholic fatty liver disease and a risk factor for cirrhosis, hepatocellular carcinoma and liver failure. Previously, we reported that dietary docosahexaenoic acid (DHA, 22:6,n-3) was more effective than eicosapentaenoic acid (EPA, 20:5,n-3) at reversing western diet (WD) induced NASH in LDLR(-/-) mice.

methodsUsing livers from our previous study, we carried out a global non-targeted metabolomic approach to quantify diet-induced changes in hepatic metabolism.

resultsLivers from WD + olive oil (WD + O)-fed mice displayed histological and gene expression features consistent with NASH. The metabolomic analysis of 320 metabolites established that the WD and n-3 polyunsaturated fatty acid (PUFA) supplementation had broad effects on all major metabolic pathways. Livers from WD + O-fed mice were enriched in saturated (SFA) and monounsaturated fatty acids (MUFA), palmitoyl-sphingomyelin, cholesterol, n-6 PUFA, n-6 PUFA-containing phosphoglycerolipids, n-6 PUFA-derived oxidized lipids (12-HETE) and depleted of C20-22 n-3 PUFA-containing phosphoglycerolipids, C20-22 n-3 PUFA-derived oxidized lipids (18-HEPE, 17,18-DiHETE) and S-lactoylglutathione, a methylglyoxal detoxification product. WD + DHA was more effective than WD + EPA at attenuating WD + O-induced changes in NASH gene expression markers, n-6 PUFA and oxidized lipids, citrate and S-lactosyl glutathione. Diet-induced changes in hepatic MUFA and sphingolipid content were associated with changes in expression of enzymes involved in MUFA and sphingolipid synthesis. Changes in hepatic oxidized fatty acids and S-lactoylglutathione, however, correlated with hepatic n-3 and n-6 C20-22 PUFA content. Hepatic C20-22 n-3 PUFA content was inversely associated with hepatic α-tocopherol and ascorbate content and positively associated with urinary F2- and F3-isoprostanes, revealing diet effects on whole body oxidative stress.

conclusionDHA regulation of hepatic SFA, MUFA, PUFA, sphingomyelin, PUFA-derived oxidized lipids and S-lactoylglutathione may explain the protective effects of DHA against WD-induced NASH in LDLR(-/-) mice.

Indexed as

DietAnimalsCarbonDisease Models, AnimalEndotoxinsEnergy MetabolismFatty AcidsFatty Acids, MonounsaturatedFatty Acids, Omega-3Fatty LiverLipid PeroxidationLiverMaleMetabolomeMetabolomicsMiceCarbonEndotoxinsFatty AcidsFatty Acids, MonounsaturatedFatty Acids, Omega-3palmitoylsphingomyelinPhospholipidsReceptors, LDLSphingomyelins

Identifiers

PMID24358308
PMCPMC3866250
OpenAlexW2046186183

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.