ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2015
Hepatocyte X-box binding protein 1 deficiency increases liver injury in mice fed a high-fat/sugar diet.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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.
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.
Who cites it
38 citing papers in PubMed, 60 citations in OpenAlex.
- Beyond fructolysis: ketohexokinase orchestrates ER proteostasis in nutrient-stressed hepatocytes.American journal of physiology. Gastrointestinal and liver physiology · 2025Article
- Identification of a Selective Pharmacologic IRE1/XBP1s Activator with Enhanced Tissue Exposure.ACS chemical biology · 2025Article
- Roles of X-box binding protein 1 in liver pathogenesis.Clinical and molecular hepatology · 2025Review
- Inhalation exposure to airborne PMAmerican journal of physiology. Cell physiology · 2025Article
- Growth Performance, Dietary Energetics, Blood Metabolites, Carcass Traits, Meat Quality, and Gene Expression of Lambs Supplemented with a Polyherbal Phytogenic Additive.Veterinary sciences · 2024Article
- Obesity disrupts the pituitary-hepatic UPR communication leading to NAFLD progression.Cell metabolism · 2024Article
- Article
- ATF4 suppresses hepatocarcinogenesis by inducing SLC7A11 (xCT) to block stress-related ferroptosis.Journal of hepatology · 2023Article
- Unboxing the cell-type specific contribution of endoplasmic reticulum stress to NASH pathophysiology-myeloid X-box-binding protein 1 as a driver of steatohepatitis and fibrosis.Translational gastroenterology and hepatology · 2023Article
- Inositol-requiring enzyme 1α/X-box protein 1 pathway expression is impaired in pediatric cholestatic liver disease explants.PloS one · 2022Article
- Article
- Mechanisms of liver injury in high fat sugar diet fed mice that lack hepatocyte X-box binding protein 1.PloS one · 2022Article
- Hepatic X-Box Binding Protein 1 and Unfolded Protein Response Is Impaired in Weanling Mice With Resultant Hepatic Injury.Hepatology (Baltimore, Md.) · 2021Article
- Xbp1s-Ddit3 promotes MCT-induced pulmonary hypertension.Clinical science (London, England : 1979) · 2021Article
- 5-Aminolevulinic Acid Attenuates Glucose-Regulated Protein 78 Expression and Hepatocyte Lipoapoptosis via Heme Oxygenase-1 Induction.International journal of molecular sciences · 2021Article
- Interferon signaling suppresses the unfolded protein response and induces cell death in hepatocytes accumulating hepatitis B surface antigen.PLoS pathogens · 2021Article
- Endoplasmic Reticulum Stress Signaling and the Pathogenesis of Hepatocarcinoma.International journal of molecular sciences · 2021Review
- Endoplasmic reticulum stress induces hepatic plasminogen activator inhibitor 1 in murine nonalcoholic steatohepatitis.FASEB bioAdvances · 2020Article
- Nonalcoholic Steatohepatitis Promoting Kinases.Seminars in liver disease · 2020Review
- Hepatic E4BP4 induction promotes lipid accumulation by suppressing AMPK signaling in response to chemical or diet-induced ER stress.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Fatty liver is associated with endoplasmic reticulum stress and activation of the hepatic unfolded protein response (UPR). Reduced hepatic expression of the UPR regulator X-box binding protein 1 spliced (XBP1s) is associated with human nonalcoholic steatohepatitis (NASH), and feeding mice a high-fat diet with fructose/sucrose causes progressive, fibrosing steatohepatitis. This study examines the role of XBP1 in nonalcoholic fatty liver injury and fatty acid-induced cell injury. Hepatocyte-specific Xbp1-deficient (Xbp1(-/-)) mice were fed a high-fat/sugar (HFS) diet for up to 16 wk. HFS-fed Xbp1(-/-) mice exhibited higher serum alanine aminotransferase levels compared with Xbp1(fl/fl) controls. RNA sequencing and Gene Ontogeny pathway analysis of hepatic mRNA revealed that apoptotic process, inflammatory response, and extracellular matrix structural constituent pathways had enhanced activation in HFS-fed Xbp1(-/-) mice. Liver histology demonstrated enhanced injury and fibrosis but less steatosis in the HFS-fed Xbp1(-/-) mice. Hepatic Col1a1 and Tgfβ1 gene expression, as well as Chop and phosphorylated JNK (p-JNK), were increased in Xbp1(-/-) compared with Xbp1(fl/fl) mice after HFS feeding. In vitro, stable XBP1-knockdown Huh7 cells (Huh7-KD) and scramble control cells (Huh7-SCR) were generated and treated with palmitic acid (PA) for 24 h. PA-treated Huh7-KD cells had increased cytotoxicity measured by lactate dehydrogenase release, apoptotic nuclei, and caspase3/7 activity assays compared with Huh7-SCR cells. CHOP and p-JNK expression was also increased in Huh7-KD cells following PA treatment. In conclusion, loss of XBP1 enhances injury in both in vivo and in vitro models of fatty liver injury. We speculate that hepatic XBP1 plays an important protective role in pathogenesis of NASH.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.