Evidence map›Paper›PMID 42398652›Full record

ArticleMolecular metabolism2026

Chronic choline restriction remodels hepatic lipid metabolism and drives insulin resistance through a CD36-ETNPPL regulatory axis.

Evan M Paules, Blake Rushing, Israel Aguilar-Ordoñez, Jose L Garduno-Hernandez, Ariana Reid, Barbara J Davis, Teodoro Bottiglieri, Karel Kalecký, Erik Lopez-Gallardo, Stephen D Hursting and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular metabolism, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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.

Evan M PaulesNutrition Research Institute, University of North Carolina at Chapel Hill, Kannapolis, NC, USA; Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Blake RushingNutrition Research Institute, University of North Carolina at Chapel Hill, Kannapolis, NC, USA; Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Israel Aguilar-OrdoñezTecnologico de Monterrey, oriGen Project, Monterrey, Nuevo Leon, Mexico.
Jose L Garduno-HernandezNutrition Research Institute, University of North Carolina at Chapel Hill, Kannapolis, NC, USA.
Ariana ReidNutrition Research Institute, University of North Carolina at Chapel Hill, Kannapolis, NC, USA.
Barbara J DavisDepartment of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Teodoro BottiglieriCenter of Metabolomics, Institute of Metabolic Disease, Baylor Scott and White Research Institute, Dallas, TX 75204, USA.
Karel KaleckýCenter of Metabolomics, Institute of Metabolic Disease, Baylor Scott and White Research Institute, Dallas, TX 75204, USA.
Erik Lopez-GallardoNutrition Research Institute, University of North Carolina at Chapel Hill, Kannapolis, NC, USA; Advanced Center for Chronic Disease (ACCDiS), Department of Biochemistry and Molecular Biology, Faculty of Chemical and Pharmaceutical Sciences & Faculty of Medicine, University of Chile, Santiago, Chile.
Stephen D HurstingNutrition Research Institute, University of North Carolina at Chapel Hill, Kannapolis, NC, USA; Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. Electronic address: hursting@email.unc.edu.
Isis Trujillo-GonzalezNutrition Research Institute, University of North Carolina at Chapel Hill, Kannapolis, NC, USA; Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. Electronic address: itruji@unc.edu.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Chronic choline insufficiency reprograms hepatic metabolism and drives insulin resistance independent of obesity. While complete choline deficiency causes liver injury, the metabolic consequences of sustained, suboptimal intake, observed in ∼90% of US adults, remain poorly defined. Here, we used integrated lipidomic, metabolomic, and transcriptomic profiling to determine how graded choline intake (0.5, 1.4, or 6.3 g/kg) regulates hepatic metabolism during a control (Con) or high-fat (HF) diet-induced obesity regimen. Under Con diets, low choline intake induced a distinct metabolic state characterized by remodeled hepatic lipid architecture, particularly within triglyceride and glycerolipid species, without altering bulk triglyceride accumulation. Mechanistically, low choline disrupted phospholipid balance and induced a coordinated, sex-dependent transcriptional response, identifying ethanolamine-phosphate phospho-lyase (ETNPPL) and the fatty acid transporter CD36 as top choline-responsive genes. These metabolic effects were unique to the Con low choline group, as a high-fat diet masked all choline-dependent variations. Specifically, ETNPPL protein abundance increased under low choline Con conditions in males but not females. Functionally, this sustained restriction led to progressive hyperglycemia and insulin resistance exclusively in male mice, whereas females remained metabolically protected. Together, these findings demonstrate that chronic choline restriction remodels hepatic lipid metabolism in the absence of obesity and define a CD36-ETNPPL axis linking choline availability to sex-specific insulin resistance.

Indexed as

CD36 AntigensCholineCholine DeficiencyInsulin ResistanceLipid MetabolismLiverAnimalsDiet, High-FatFemaleMaleMiceMice, Inbred C57BLObesityCD36 AntigensCd36 protein, mouseCholineCd36CholineETNPPLInsulin resistanceMetabolic syndrome

Identifiers

PMID42398652
PMCPMC13382129

What Socratic holds

Textmetadata
LicenceCC BY
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.