Evidence map›Paper›PMID 24507550›Full record

ArticleGastroenterology2014

MicroRNA 375 mediates palmitate-induced enteric neuronal damage and high-fat diet-induced delayed intestinal transit in mice.

Behtash Ghazi Nezami, Simon M Mwangi, Jai Eun Lee, Sabrina Jeppsson, Mallappa Anitha, Shadi S Yarandi, Alton B Farris, Shanthi Srinivasan

Open access · greenAbstract read
In one paragraph

Article in Gastroenterology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
69citing papers in PubMed, 1 pooled it
5.5field-weighted citation impact, top 4% 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

69 citing papers in PubMed, 1 synthesis or guideline pooled it, 120 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Treatment with saponins fromNutrition research and practice · 2026
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9 more citing papers are in PubMed but not listed here.

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

8 authors at 2 institutions in 1 country.

Behtash Ghazi NezamiDepartment of Digestive Diseases, Emory University School of Medicine, Atlanta, Georgia; Atlanta VA Medical Center, Decatur, Georgia.
Simon M MwangiDepartment of Digestive Diseases, Emory University School of Medicine, Atlanta, Georgia; Atlanta VA Medical Center, Decatur, Georgia.
Jai Eun LeeDepartment of Digestive Diseases, Emory University School of Medicine, Atlanta, Georgia; Atlanta VA Medical Center, Decatur, Georgia.
Sabrina JeppssonDepartment of Digestive Diseases, Emory University School of Medicine, Atlanta, Georgia; Atlanta VA Medical Center, Decatur, Georgia.
Mallappa AnithaDepartment of Digestive Diseases, Emory University School of Medicine, Atlanta, Georgia; Atlanta VA Medical Center, Decatur, Georgia.
Shadi S YarandiDepartment of Digestive Diseases, Emory University School of Medicine, Atlanta, Georgia; Atlanta VA Medical Center, Decatur, Georgia.
Alton B FarrisDepartment of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia.
Shanthi SrinivasanDepartment of Digestive Diseases, Emory University School of Medicine, Atlanta, Georgia; Atlanta VA Medical Center, Decatur, Georgia. Electronic address: ssrini2@emory.edu.
Atlanta VA Medical Center · USEmory University · US

Funding

Mechanism of Enteric NeuropathyR01DK080684 · NIDDK · EMORY UNIVERSITY · PI Shanthi K Srinivasan · 2009 to 2026
$6.1M
NIDDK NIH HHS R01 DK080684NIDDK NIH HHS R01-DK080684
6 · The paper itself

Abstract

BACKGROUND &

aimsA high-fat diet (HFD) can cause serious health problems, including alteration of gastrointestinal transit, the exact mechanism of which is not clear. Several microRNAs (miRNAs) are involved in energy homeostasis, lipid metabolism, and HFD-induced weight gain. We investigated the role of miRNAs in HFD-induced damage to the enteric nervous system.

methodsMale mice were fed a HFD (60% calories from fat) or regular diets (18% calories from fat) for 11 weeks. Mice on regular diets and HFDs were given intraperitoneal injections of Mir375 inhibitor or a negative control. Body weights, food intake, stool indices, and gastrointestinal transit (following Evans blue gavage) were measured. An enteric neuronal cell line (immorto-fetal enteric neuronal) and primary enteric neurons were used for in vitro studies.

resultsHFD delayed intestinal transit, which was associated with increased apoptosis and loss of colonic myenteric neurons. Mice fed a low-palmitate HFD did not develop a similar phenotype. Palmitate caused apoptosis of enteric neuronal cells associated with mitochondrial dysfunction and endoplasmic reticulum stress. Palmitate significantly increased the expression of Mir375 in vitro; transfection of cells with a Mir375 inhibitor prevented the palmitate-induced enteric neuronal cell apoptosis. Mir375 expression was increased in myenteric ganglia of mice fed HFD and associated with decreased levels of Mir375 target messenger RNAs, including Pdk1. Systemic injection of a Mir375 inhibitor for 5 weeks prevented HFD-induced delay in intestinal transit and morphologic changes.

conclusionsHFDs delay colonic transit, partly by inducing apoptosis in enteric neuronal cells. This effect is mediated by Mir375 and is associated with reduced levels of Pdk1. Mir375 might be targeted to increase survival of enteric neurons and gastrointestinal motility.

Indexed as

AnimalsApoptosisBiomarkersCell LineColonDietary FatsDiet, High-FatEnteric Nervous SystemGastrointestinal TransitMaleMiceMice, Inbred C57BLMicroRNAsNeuronsPalmitatesProtein Serine-Threonine KinasesBiomarkersDietary FatsMicroRNAsMirn375 microRNA, mousePalmitatesPdk1 protein, mouseProtein Serine-Threonine KinasesPyruvate Dehydrogenase Acetyl-Transferring Kinase3-phosphoinositide-dependent protein kinase-1ChATcholine acetyltransferaseendoplasmic reticulumENSenteric nervous systemERFFAsFITCfluorescein isothiocyanatefree fatty acidsgastrointestinalGastrointestinalGIHFDhigh-fat dietHyperlipidemialow-palmitate HFDLP-HFDmessenger RNAmicroRNAsMicroRNAsmiRNAsMotilitymRNANADPH diaphorasenicotinamide adenine dinucleotide phosphatePdk1RDregular dietSODsuperoxide dismutase

Identifiers

PMID24507550
PMCPMC3920196
OpenAlexW2122244729

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.