ArticleJCI insight2018
Hepatocyte ALOXE3 is induced during adaptive fasting and enhances insulin sensitivity by activating hepatic PPARγ.
Article in JCI insight, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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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.
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Who cites it
19 citing papers in PubMed, 33 citations in OpenAlex.
- RNF128 regulates the adaptive metabolic response to fasting by modulating PPARα function.Cell death and differentiation · 2026Article
- Targeting hepatocyte-specific SLC2A8 blocks hepatic steatosis and dissociates TCA cycle flux inhibition from glutamine anaplerosis.Hepatology communications · 2025Article
- ALOXE3 expression predicts poor prognosis and modulates immune infiltration in colon adenocarcinoma.World journal of surgical oncology · 2025Article
- Rodent Diets Incorporated with Live Biotherapeutic Products (LBPs): An Innovative Dosing Strategy to Support Preclinical Animal Studies on LBP Intervention.AAPS PharmSciTech · 2025Article
- Hepatocyte Period 1 dictates oxidative substrate selection independent of the core circadian clock.Cell reports · 2024Article
- Hepatocyte MMP14 mediates liver and inter-organ inflammatory responses to diet-induced liver injury.PNAS nexus · 2024Article
- Intracellular Protective Functions and Therapeutical Potential of Trehalose.Molecules (Basel, Switzerland) · 2024Review
- Review
- The tetraspanin transmembrane protein CD53 mediates dyslipidemia and integrates inflammatory and metabolic signaling in hepatocytes.The Journal of biological chemistry · 2023Article
- Pegylated arginine deiminase drives arginine turnover and systemic autophagy to dictate energy metabolism.Cell reports. Medicine · 2022Article
- Targeting hepatocyte carbohydrate transport to mimic fasting and calorie restriction.The FEBS journal · 2021Review
- miR-18a promotes glioblastoma development by down-regulating ALOXE3-mediated ferroptotic and anti-migration activities.Oncogenesis · 2021Article
- The role of chemoenzymatic synthesis in advancing trehalose analogues as tools for combatting bacterial pathogens.Chemical communications (Cambridge, England) · 2020Article
- Microbial and metabolic impacts of trehalose and trehalose analogues.Gut microbes · 2020Article
- Lactotrehalose, an Analog of Trehalose, Increases Energy Metabolism Without Promoting Clostridioides difficile Infection in Mice.Gastroenterology · 2020Article
- Using trehalose to prevent and treat metabolic function: effectiveness and mechanisms.Current opinion in clinical nutrition and metabolic care · 2019Review
- Degradation-resistant trehalose analogues block utilization of trehalose by hypervirulent Clostridioides difficile.Chemical communications (Cambridge, England) · 2019Article
- Hepatic arginase 2 (Arg2) is sufficient to convey the therapeutic metabolic effects of fasting.Nature communications · 2019Article
- Activation of ectopic olfactory receptor 544 induces GLP-1 secretion and regulates gut inflammation.Gut microbesArticle
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
The hepatic glucose fasting response is gaining traction as a therapeutic pathway to enhance hepatic and whole-host metabolism. However, the mechanisms underlying these metabolic effects remain unclear. Here, we demonstrate the epidermal-type lipoxygenase, eLOX3 (encoded by its gene, Aloxe3), is a potentially novel effector of the therapeutic fasting response. We show that Aloxe3 is activated during fasting, glucose withdrawal, or trehalose/trehalose analogue treatment. Hepatocyte-specific Aloxe3 expression reduced weight gain and hepatic steatosis in diet-induced and genetically obese (db/db) mouse models. Aloxe3 expression, moreover, enhanced basal thermogenesis and abrogated insulin resistance in db/db diabetic mice. Targeted metabolomics demonstrated accumulation of the PPARγ ligand 12-KETE in hepatocytes overexpressing Aloxe3. Strikingly, PPARγ inhibition reversed hepatic Aloxe3-mediated insulin sensitization, suppression of hepatocellular ATP production and oxygen consumption, and gene induction of PPARγ coactivator-1α (PGC1α) expression. Moreover, hepatocyte-specific PPARγ deletion reversed the therapeutic effect of hepatic Aloxe3 expression on diet-induced insulin intolerance. Aloxe3 is, therefore, a potentially novel effector of the hepatocellular fasting response that leverages both PPARγ-mediated and pleiotropic effects to augment hepatic and whole-host metabolism, and it is, thus, a promising target to ameliorate metabolic disease.
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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.