Evidence mapPaperPMID 41736066Full record

ArticleLipids in health and disease2026

4-phenylbutyric acid attenuates hepatic ER stress, pyroptosis, and NAFLD in adult rat offspring exposed to a high-fat, high-fructose diet during perinatal and adulthood.

Sara Ojaghi, Farzaneh Eskandari, Fariba Azarkish, Haniyeh Soltani, Fateme Binayi, Behnam Saeidi, Mehdi Hedayati, Afsaneh Goudarzi, Abdollah Amini, Fariba Khodagholi and 1 more

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Article in Lipids in health and disease, 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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2 · The registry

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4 · The record

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5 · Who and what money

Authors and funding

11 authors.

Sara OjaghiDepartment of Clinical Biochemistry, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Farzaneh EskandariNeurophysiology Research Center, Institute of Neuroscience and Cognition, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Fariba AzarkishDepartment of Physiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Haniyeh SoltaniDepartment of Physiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Fateme BinayiGastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Behnam SaeidiDepartment of Research and Development, Razi Vaccine and Serum Research Institute, Agricultural Research, Education and Extension Organization (AREEO), P.O. Box 31975/148, Karaj, Iran.
Mehdi HedayatiCellular and Molecular Endocrine Research Center, Research Institute for Endocrine Molecular Biology, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Afsaneh GoudarziDepartment of Clinical Biochemistry, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Abdollah AminiDepartment of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Fariba KhodagholiNeuroscience Research Center, Institute of Neuroscience and Cognition, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Homeira ZardoozNeurophysiology Research Center, Institute of Neuroscience and Cognition, Shahid Beheshti University of Medical Sciences, Tehran, Iran. homeira_zardooz@sbmu.ac.ir.

Funding

Shahid Beheshti University of Medical Sciences 43008299
6 · The paper itself

Abstract

backgroundPerinatal exposure to high-fat and/or high-fructose diets affects offspring metabolic programming, increasing the risk of metabolic disorders such as non-alcoholic fatty liver disease (NAFLD). In addition, re-exposure to these diets during adulthood exacerbates metabolic disturbances, indicating an interaction between early- and later-life diets in disease development. Therefore, the present study was designed to assess the effects of high-fat, high-fructose (HFF) diet exposure during the perinatal period and adulthood on hepatic endoplasmic reticulum (ER) stress, pyroptosis, and NAFLD development, as well as to evaluate the potential therapeutic effects of 4-phenylbutyric acid (4-PBA).

methodsMale rat offspring were randomly assigned to six groups based on perinatal and adulthood diets: normal diet during both periods (N-N), normal perinatal diet with adulthood HFF diet (N-HFF), perinatal HFF diet with normal adulthood diet (HFF-N), perinatal and adulthood HFF diet (HFF-HFF), perinatal and adulthood HFF diet with DMSO treatment (HFF-HFF-DMSO), and perinatal and adulthood HFF diet with 4-PBA treatment (HFF-HFF-4PBA). Metabolic parameters, inflammatory markers, oxidative and ER stress indicators, a pyroptosis marker, and hepatic histological parameters were evaluated.

resultsExposure to the HFF diet during the perinatal period and adulthood induced insulin resistance, dyslipidemia, hepatic oxidative and ER stress, inflammation, pyroptosis, lipid droplet accumulation, and NAFLD development. Treatment with 4-PBA improved all adverse effects caused by HFF diet exposure during both the perinatal and adult periods in offspring.

conclusionThese findings highlight the importance of dietary interventions during critical developmental windows and suggest ER stress inhibition as a promising therapeutic approach for NAFLD.

Indexed as

Diet, High-FatEndoplasmic Reticulum StressFructoseNon-alcoholic Fatty Liver DiseasePhenylbutyratesPrenatal Exposure Delayed EffectsPyroptosisAnimalsDevelopmental Origins of Health and DiseaseFemaleLiverMalePregnancyRats4-phenylbutyric acidFructosePhenylbutyrates4-phenylbutyric acidEndoplasmic reticulum stressHigh-fat, high-fructose dietNonalcoholic fatty liver diseasePerinatal and adulthoodPyroptosis

Identifiers

PMID41736066
PMCPMC13037004

What Socratic holds

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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 Socratic graph.