Evidence map›Paper›PMID 26511317›Full record

ArticleThe Journal of biological chemistry2016

Insulin Dissociates the Effects of Liver X Receptor on Lipogenesis, Endoplasmic Reticulum Stress, and Inflammation.

Xiaowei Sun, Mary E Haas, Ji Miao, Abhiruchi Mehta, Mark J Graham, Rosanne M Crooke, Jean-Paul Pais de Barros, Jian-Guo Wang, Masanori Aikawa, David Masson and 1 more

Open access · hybridAbstract readComparative Study
In one paragraph

Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
2.1field-weighted citation impact, top 13% 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

13 citing papers in PubMed, 21 citations in OpenAlex.

  1. Insight into the Hypoglycemic Effects ofPlants (Basel, Switzerland) · 2026
    Article
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  6. Review
  7. Article
  8. Article
  9. The Antagonist Effect of Arachidonic Acid onInternational journal of molecular sciences · 2019
    Article
  10. G0S2: A small giant controller of lipolysis and adipose-liver fatty acid flux.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2017
    Review
  11. Liver X receptorJCI insight · 2017
    Article
  12. Article
  13. Article
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

11 authors at 5 institutions in 2 countries.

Xiaowei SunFrom the Division of Endocrinology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115.
Mary E HaasFrom the Division of Endocrinology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115.
Ji MiaoFrom the Division of Endocrinology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115.
Abhiruchi MehtaFrom the Division of Endocrinology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115.
Mark J GrahamIsis Pharmaceuticals, Carlsbad, California 92008.
Rosanne M CrookeIsis Pharmaceuticals, Carlsbad, California 92008.
Jean-Paul Pais de Barrosthe Centre de Recherche INSERM-UMR866, Université de Bourgogne, 21000 Dijon, France, and.
Jian-Guo Wangthe Center for Interdisciplinary Cardiovascular Sciences, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115.
Masanori Aikawathe Center for Interdisciplinary Cardiovascular Sciences, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115.
David Massonthe Centre de Recherche INSERM-UMR866, Université de Bourgogne, 21000 Dijon, France, and.
Sudha B BiddingerFrom the Division of Endocrinology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, sudha.biddinger@childrens.harvard.edu.
Harvard University · USBoston Children's Hospital · USCentre de recherche Translationnelle en Médecine moléculaire · FRIonis Pharmaceuticals (United States) · USBrigham and Women's Hospital · US

Funding

Control of lipid metabolism in insulin resistant statesR01DK094162 · NIDDK · BOSTON CHILDREN'S HOSPITAL · PI BIDDINGER, SUDHA B · 2012 to 2015
$1.5M
Insulin Regulation of Liver X Receptor in Normal and Insulin Resistant StatesR00DK100539 · NIDDK · BOSTON CHILDREN'S HOSPITAL · PI MIAO, JI · 2016 to 2018
$747k
Insulin Regulation of Liver X Receptor in Normal and Insulin Resistant StatesK99DK100539 · NIDDK · BOSTON CHILDREN'S HOSPITAL · PI MIAO, JI · 2013 to 2014
$180k
NIDDK NIH HHS DK094162NIDDK NIH HHS DK100539NIDDK NIH HHS K99 DK100539NIDDK NIH HHS L40 DK065607NIDDK NIH HHS R00 DK100539NIDDK NIH HHS R01 DK094162
6 · The paper itself

Abstract

Diabetes is characterized by increased lipogenesis as well as increased endoplasmic reticulum (ER) stress and inflammation. The nuclear hormone receptor liver X receptor (LXR) is induced by insulin and is a key regulator of lipid metabolism. It promotes lipogenesis and cholesterol efflux, but suppresses endoplasmic reticulum stress and inflammation. The goal of these studies was to dissect the effects of insulin on LXR action. We used antisense oligonucleotides to knock down Lxrα in mice with hepatocyte-specific deletion of the insulin receptor and their controls. We found, surprisingly, that knock-out of the insulin receptor and knockdown of Lxrα produced equivalent, non-additive effects on the lipogenic genes. Thus, insulin was unable to induce the lipogenic genes in the absence of Lxrα, and LXRα was unable to induce the lipogenic genes in the absence of insulin. However, insulin was not required for LXRα to modulate the phospholipid profile, or to suppress genes in the ER stress or inflammation pathways. These data show that insulin is required specifically for the lipogenic effects of LXRα and that manipulation of the insulin signaling pathway could dissociate the beneficial effects of LXR on cholesterol efflux, inflammation, and ER stress from the negative effects on lipogenesis.

Indexed as

Endoplasmic Reticulum StressGene Expression RegulationLipogenesisAnimalsCrosses, GeneticDiabetes Mellitus, Type 2FemaleGene Expression Regulation, EnzymologicGene Knockdown TechniquesHepatitisInsulinInsulin ResistanceLiverLiver X ReceptorsMice, Inbred C57BLMice, KnockoutInsulinLiver X ReceptorsNr1h3 protein, mouseOrphan Nuclear ReceptorsPhospholipidsReceptor, Insulinendoplasmic reticulum stress (ER stress)fructoseinflammationinsulininsulin resistancelipid metabolismlipogenesisliver insulin-receptor knockoutliver X receptorlysophosphatidylcholine acyltransferase 3phospholipidphospholipid metabolismselective insulin resistance

Identifiers

PMID26511317
PMCPMC4714195
OpenAlexW2238121838

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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 Socratic graph.