ArticleDiabetologia2013
Fatty acids differentially regulate insulin resistance through endoplasm reticulum stress-mediated induction of tribbles homologue 3: a potential link between dietary fat composition and the pathophysiological outcomes of obesity.
Article in Diabetologia, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 45 citations in OpenAlex.
- Loss of ceramide synthases 5 and 6 exacerbate myristate-induced colonic IRE1α activation.Journal of lipid research · 2026Article
- Glutamine Deprivation Triggers Tribbles Homolog 3 Dependent G-Quadruplex Resolution to Maintain DNA Repair and Tumor Survival.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Multiomics reveals changes in lipid metabolism in the livers of Landes geese before and after overfeeding.Animal bioscience · 2026Article
- Effects of Nutritional Disturbances on the Structure and Function of Mitochondria, Oxidative Stress Level, and Fat Deposition in Chicken Liver Cells.Animals : an open access journal from MDPI · 2025Article
- Diet-induced obesity and aging-induced upregulation of Trib3 interfere with energy homeostasis by downregulating the thermogenic capacity of BAT.Experimental & molecular medicine · 2024Article
- Lipotoxicity of palmitic acid is associated with DGAT1 downregulation and abolished by PPARα activation in liver cells.Journal of lipid research · 2024Article
- SGLT2 inhibition leads to a restoration of hepatic and circulating metabolites involved in the folate cycle and pyrimidine biosynthesis.American journal of physiology. Gastrointestinal and liver physiology · 2024Article
- Nascent shifts in renal cellular metabolism, structure, and function due to chronic empagliflozin in prediabetic mice.American journal of physiology. Cell physiology · 2024Article
- Integration of dietary nutrition and TRIB3 action into diabetes mellitus.Nutrition reviews · 2024Review
- Protein Kinases in Obesity, and the Kinase-Targeted Therapy.Advances in experimental medicine and biology · 2024Review
- Effect of Lard or Plus Soybean Oil on Markers of Liver Function in Healthy Subjects: A Randomized Controlled-Feeding Trial.Foods (Basel, Switzerland) · 2023Article
- Renal Metabolome in Obese Mice Treated with Empagliflozin Suggests a Reduction in Cellular Respiration.Biomolecules · 2022Article
- Sphingosine kinase 1 mediates sexual dimorphism in fibrosis in a mouse model of NASH.Molecular metabolism · 2022Article
- Empagliflozin Treatment Attenuates Hepatic Steatosis by Promoting White Adipose Expansion in Obese TallyHo Mice.International journal of molecular sciences · 2022Article
- Article
- Review
- Fasting and overfeeding affect the expression of the immunity- or inflammation-related genes in the liver of poultry via endogenous retrovirus.Poultry science · 2021Article
- Current perspectives of oleic acid: Regulation of molecular pathways in mitochondrial and endothelial functioning against insulin resistance and diabetes.Reviews in endocrine & metabolic disorders · 2020Review
- UHPLC/QTOF-MS-based metabolomics reveal the effect ofPharmaceutical biology · 2019Article
- Myristate-induced endoplasmic reticulum stress requires ceramide synthases 5/6 and generation of C14-ceramide in intestinal epithelial cells.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2018Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisPrevious studies have shown that saturated fatty acids cause insulin resistance (IR) that is prevented by unsaturated fatty acids. Tribbles homologue 3 (TRIB3) is a putative endogenous inhibitor of insulin signalling, but its role in insulin signalling is controversial. This study aimed to determine whether fatty acids regulate IR via TRIB3.
methodsWe treated HepG2 cells with saturated and unsaturated fatty acids and evaluated TRIB3 expression. We then tested whether regulation of TRIB3 occurred through endoplasmic reticulum (ER) stress, and whether modulating TRIB3 and ER stress marker genes was necessary and/or sufficient for regulation of insulin signalling. To test the in vivo significance of this mechanism, we fed mice obesogenic diets with different fatty acid profiles and assessed physiological variables of diabetes, ER stress markers and Trib3 expression in the liver.
resultsOur data show that fatty acids differentially regulate IR through ER stress-mediated induction of TRIB3. Intriguingly, a standard and widely used obesogenic diet high in unsaturated fats failed to induce ER stress, TRIB3 or IR. However, an alternative obesogenic diet with lower unsaturated fat recapitulated the cell studies by causing ER stress, TRIB3 induction and IR. CONCLUSIONS/
interpretationThis study revealed a novel mechanism linking dietary fat composition to IR. Given the emerging roles for ER stress in non-alcoholic liver disease, we conclude that dietary fat composition rather than total amount may mediate hepatic pathology associated with obesity.
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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.