Evidence map›Paper›PMID 26007286›Full record

ArticleThe Journal of nutritional biochemistry2015

Activation of hepatic CREBH and Insig signaling in the anti-hypertriglyceridemic mechanism of R-α-lipoic acid.

Xuedong Tong, Patricia Christian, Miaoyun Zhao, Hai Wang, Regis Moreau, Qiaozhu Su

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of nutritional biochemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.9field-weighted citation impact, top 27% 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

5 citing papers in PubMed, 16 citations in OpenAlex.

  1. Review
  2. Article
  3. Biomedicines · 2020
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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

6 authors at 2 institutions in 2 countries.

Xuedong TongKey Laboratory of Laboratory Medicine, Zhejiang Provincial Key Laboratory of Medical Genetics, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China; Department of Nutrition and Health Sciences, University of Nebraska Lincoln, Lincoln, NE 68583-0806, USA.
Patricia ChristianDepartment of Nutrition and Health Sciences, University of Nebraska Lincoln, Lincoln, NE 68583-0806, USA.
Miaoyun ZhaoDepartment of Nutrition and Health Sciences, University of Nebraska Lincoln, Lincoln, NE 68583-0806, USA.
Hai WangDepartment of Nutrition and Health Sciences, University of Nebraska Lincoln, Lincoln, NE 68583-0806, USA.
Regis MoreauDepartment of Nutrition and Health Sciences, University of Nebraska Lincoln, Lincoln, NE 68583-0806, USA.
Qiaozhu SuDepartment of Nutrition and Health Sciences, University of Nebraska Lincoln, Lincoln, NE 68583-0806, USA. Electronic address: qsu2@unl.edu.
University of Nebraska–Lincoln · USWenzhou Medical University · CN

Funding

The role of stress in the fetal origin of obesity and metabolic dysfunctionP20GM104320 · NIGMS · UNIVERSITY OF NEBRASKA LINCOLN · PI ZEMPLENI, JANOS · 2014 to 2024
$24.9M
NIGMS NIH HHS P20 GM104320NIGMS NIH HHS P20 GM104320-01A1
6 · The paper itself

Abstract

The activation of sterol regulatory element binding proteins (SREBPs) is regulated by insulin-induced genes 1 and 2 (Insig-1 and Insig-2) and SCAP. We previously reported that feeding R-α-lipoic acid (LA) to Zucker diabetic fatty (ZDF) rats improves severe hypertriglyceridemia. In this study, we investigated the role of cyclic AMP-responsive element binding protein H (CREBH) in the lipid-lowering mechanism of LA and its involvement in the SREBP-1c and Insig pathway. Incubation of McA cells with LA (0.2 mM) or glucose (6 mM) stimulated activation of CREBH. LA treatment further induced mRNA expression of Insig-1 and Insig-2a, but not Insig-2b, in glucose-treated cells. In vivo, feeding LA to obesity-induced hyperlipidemic ZDF rats activated hepatic CREBH and stimulated transcription and translation of Insig-1 and Insig-2a. Activation of CREBH and Insigs induced by LA suppressed processing of SREBP-1c precursor into nuclear SREBP-1c, which subsequently inhibited expression of genes involved in fatty acid synthesis, including FASN, ACC and SCD-1, and reduced triglyceride (TG) contents in both glucose-treated cells and ZDF rat livers. Additionally, LA treatment also decreased abundances of very low density lipoprotein (VLDL)-associated apolipoproteins, apoB100 and apoE, in glucose-treated cells and livers of ZDF rats, leading to decreased secretion of VLDL and improvement of hypertriglyceridemia. This study unveils a novel molecular mechanism whereby LA lowers TG via activation of hepatic CREBH and increased expression of Insig-1 and Insig-2a to inhibit de novo lipogenesis and VLDL secretion. These findings provide novel insight into the therapeutic potential of LA as an anti-hypertriglyceridemia dietary molecule.

Indexed as

Dietary SupplementsAlternative SplicingAnimalsCell Line, TumorCyclic AMP Response Element-Binding ProteinHepatocytesHypertriglyceridemiaHypolipidemic AgentsIntracellular Signaling Peptides and ProteinsLipoproteins, VLDLMaleMembrane ProteinsProtein Processing, Post-TranslationalRandom AllocationRats, Inbred BUFRats, ZuckerCreb3l3 protein, ratCyclic AMP Response Element-Binding ProteinHypolipidemic AgentsInsig1 protein, ratInsig2 protein, ratIntracellular Signaling Peptides and ProteinsLipoproteins, VLDLMembrane ProteinsSrebf1 protein, ratSterol Regulatory Element Binding Protein 1Thioctic AcidApolipoproteinsCell signalingDyslipidemiasSterol regulatory element binding proteinsTriglyceride metabolismVery low density lipoprotein

Identifiers

PMID26007286
PMCPMC4547883
OpenAlexW1540565773

What OpenQuestion holds

Textmetadata
LicenceTDM
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 OpenQuestion graph.