Evidence map›Paper›PMID 42398653›Full record

ArticleMolecular metabolism2026

Metabolite-driven remodeling of hepatic lipid metabolism by the plasticizer di-isononyl phthalate.

Sini Pitkänen, Henriikka Hakomäki, Olli Kärkkäinen, Marko Lehtonen, Sreejita Das, Jaana Rysä, Jenni Küblbeck, Anna-Liisa Levonen

Abstract read
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.

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1 · What the graph read from it

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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

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

8 authors.

Sini PitkänenA. I. Virtanen -institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
Henriikka HakomäkiA. I. Virtanen -institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
Olli KärkkäinenSchool of Pharmacy, University of Eastern Finland, Kuopio, Finland.
Marko LehtonenSchool of Pharmacy, University of Eastern Finland, Kuopio, Finland.
Sreejita DasA. I. Virtanen -institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
Jaana RysäSchool of Pharmacy, University of Eastern Finland, Kuopio, Finland.
Jenni KüblbeckA. I. Virtanen -institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland; School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
Anna-Liisa LevonenA. I. Virtanen -institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland. Electronic address: anna-liisa.levonen@uef.fi.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionPhthalates are widely used as plasticizers in consumer products and are suspected to be metabolism-disrupting chemicals. Di-isononyl phthalate (DINP) is commonly recognized as less hazardous substitute for more studied di(2-ethylhexyl) phthalate (DEHP). MATERIALS AND

methodsThe effects of DINP on hepatic lipid metabolism were studied using C57BL/6J mice with diet-induced obesity, and human HepaRG and C3A cell lines. The mice were orally exposed to 0, 1.5, 15 or 150 mg/kg bw/d DINP for 20 weeks, followed by assessment of glucose and insulin tolerance, hepatic histology, transcriptome and metabolome. The cells were exposed to DINP and its metabolites, followed by measurement of mitochondrial function and nuclear receptor activation.

resultsThe highest dose of DINP decreased hepatic lipid droplets and slightly attenuated weight gain and glucose tolerance of the mice. DINP exposure elevated acylcarnitine levels, indicating altered fatty acid beta-oxidation, which was accompanied by enrichment in mitochondrial and peroxisomal lipid metabolism pathways at transcriptomics level. In vitro, monoisononyl phthalate (MINP), the primary metabolite of DINP, increased mitochondrial respiration and beta-oxidation in presence of long-chain fatty acids. DINP metabolites activated peroxisome proliferator-activated receptors (PPARs) of both mouse and human, with an activation profile partially distinct from DEHP.

conclusionsOur findings indicate that DINP remodels hepatic lipid metabolism through its active metabolites via PPARs at high doses, with additional modes of action at lower exposure levels. Due to species-specific differences in nuclear receptor activation potencies, the adverse or potentially beneficial nature of these effects in humans remains ambiguous.

Indexed as

Lipid MetabolismLiverPhthalic AcidsPlasticizersAnimalsHumansMaleMiceMice, Inbred C57BLMitochondriaObesitydiisononyl phthalatePhthalic AcidsPlasticizersDi-isononyl phthalateLipid metabolismLiverMetabolism-disrupting chemicalMitochondria

Identifiers

PMID42398653
PMCPMC13382126

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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.