ArticleThe Journal of biological chemistry2013
ATF4 protein deficiency protects against high fructose-induced hypertriglyceridemia in mice.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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Who cites it
73 citing papers in PubMed, 140 citations in OpenAlex.
- ATF4: Orchestrating Cellular Stress Adaptation, Metabolism, and Immune Regulation in Health and Disease.International journal of molecular sciences · 2026Review
- Understanding Liver and Digestive Diseases: A Paved Road to Improve Diagnosis, Management, and Treatment.Exploration of digestive diseases · 2026Article
- AP-1 elements in the promoter and second intron mediate endoplasmic reticulum stress-induced expression of the GPAT3 gene.Scientific reports · 2025Article
- An ATF3 Inducer Ameliorates Metabolic Dysfunction-Associated Steatotic Liver Disease Through the AMPK and PKA Pathways.International journal of molecular sciences · 2025Article
- Altered Expression of theNutrients · 2025Article
- Article
- Lack of adipocyte FAM20C improves whole body glucose homeostasis.Physiological reports · 2024Article
- Gut-derived ammonia contributes to alcohol-related fatty liver development via facilitating ethanol metabolism and provoking ATF4-dependent de novo lipogenesis activation.Metabolism: clinical and experimental · 2024Article
- Hugan Qingzhi tablets attenuates endoplasmic reticulum stress in nonalcoholic fatty liver disease rats by regulating PERK and ATF6 pathways.BMC complementary medicine and therapies · 2024Article
- The Role of Endoplasmic Reticulum in Lipotoxicity during Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) Pathogenesis.The American journal of pathology · 2023Review
- Dose-effect of polystyrene microplastics on digestive toxicity in chickens (Gallus gallus): Multi-omics reveals critical role of gut-liver axis.Journal of advanced research · 2023Article
- Ufmylation on UFBP1 alleviates non-alcoholic fatty liver disease by modulating hepatic endoplasmic reticulum stress.Cell death & disease · 2023Article
- More than meets the eye in Parkinson's disease and other synucleinopathies: from proteinopathy to lipidopathy.Acta neuropathologica · 2023Review
- ATF4 suppresses hepatocarcinogenesis by inducing SLC7A11 (xCT) to block stress-related ferroptosis.Journal of hepatology · 2023Article
- Ectopic Lipid Accumulation Correlates with Cellular Stress in Rabbit Blastocysts from Diabetic Mothers.International journal of molecular sciences · 2023Article
- miR-27b targets MAIP1 to mediate lipid accumulation in cultured human and mouse hepatic cells.Communications biology · 2023Article
- Opposite modulation of functional recovery following contusive spinal cord injury in mice with oligodendrocyte-selective deletions of Atf4 and Chop/Ddit3.Scientific reports · 2023Article
- Glucokinase activator improves glucose tolerance and induces hepatic lipid accumulation in mice with diet-induced obesity.Liver research (Beijing, China) · 2023Article
- Review
- Mitochondrial remodelling is essential for female germ cell differentiation and survival.PLoS genetics · 2023Article
13 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
Hypertriglyceridemia is the most common lipid disorder in obesity and type 2 diabetes. It results from increased production and/or decreased clearance of triglyceride-rich lipoproteins. To better understand the pathophysiology of hypertriglyceridemia, we studied hepatic regulation of triglyceride metabolism by the activating transcription factor 4 (ATF4), a member of the basic leucine zipper-containing protein subfamily. We determined the effect of ATF4 on hepatic lipid metabolism in Atf4(-/-) mice fed regular chow or provided with free access to fructose drinking water. ATF4 depletion preferentially attenuated hepatic lipogenesis without affecting hepatic triglyceride production and fatty acid oxidation. This effect prevented excessive fat accumulation in the liver of Atf4(-/-) mice, when compared with wild-type littermates. To gain insight into the underlying mechanism, we showed that ATF4 depletion resulted in a significant reduction in hepatic expression of peroxisome proliferator-activated receptor-γ, a nuclear receptor that acts to promote lipogenesis in the liver. This effect was accompanied by a significant reduction in hepatic expression of sterol regulatory element-binding protein 1c (SREBP-1c), acetyl-CoA carboxylase, and fatty-acid synthase, three key functions in the lipogenic pathway in Atf4(-/-) mice. Of particular significance, we found that Atf4(-/-) mice, as opposed to wild-type littermates, were protected against the development of steatosis and hypertriglyceridemia in response to high fructose feeding. These data demonstrate that ATF4 plays a critical role in regulating hepatic lipid metabolism in response to nutritional cues.
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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.