ArticleBiochemical pharmacology2016
Fenretinide mediated retinoic acid receptor signalling and inhibition of ceramide biosynthesis regulates adipogenesis, lipid accumulation, mitochondrial function and nutrient stress signalling in adipocytes and adipose tissue.
Article in Biochemical pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 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
21 citing papers in PubMed, 41 citations in OpenAlex.
- Adipocyte Browning: A Promising Avenue in Anti-Obesity Therapy.International journal of molecular sciences · 2026Review
- Unraveling the Causal Linkages ofBioMed research international · 2026Article
- A New Strategy for Obesity Treatment: Revealing the Frontiers of Anti-obesity Medications.Current molecular medicine · 2025Review
- Thermogenic Fat as a New Obesity Management Tool: From Pharmaceutical Reagents to Cell Therapies.Biomedicines · 2024Review
- International Union of Basic and Clinical Pharmacology CXIII: Nuclear Receptor Superfamily-Update 2023.Pharmacological reviews · 2023Review
- Fenretinide inhibits obesity and fatty liver disease but induces Smpd3 to increase serum ceramides and worsen atherosclerosis in LDLRScientific reports · 2023Article
- Monascuspiloin fromFoods (Basel, Switzerland) · 2022Article
- Dihydroceramide Desaturase Functions as an Inducer and Rectifier of Apoptosis: Effect of Retinol Derivatives, Antioxidants and Phenolic Compounds.Cell biochemistry and biophysics · 2021Article
- CFTR Correctors and Antioxidants Partially Normalize Lipid Imbalance but not Abnormal Basal Inflammatory Cytokine Profile in CF Bronchial Epithelial Cells.Frontiers in physiology · 2021Article
- Dietary Folic Acid Alters Metabolism of Multiple Vitamins in a CerS6- and Sex-Dependent Manner.Frontiers in nutrition · 2021Article
- Human skeletal muscle metabolic responses to 6 days of high-fat overfeeding are associated with dietary n-3PUFA content and muscle oxidative capacity.Physiological reports · 2020Article
- Fenretinide treatment accelerates atherosclerosis development in apoE-deficient mice in spite of beneficial metabolic effects.British journal of pharmacology · 2020Article
- β-carotene in Obesity Research: Technical Considerations and Current Status of the Field.Nutrients · 2019Review
- Small molecules for fat combustion: targeting obesity.Acta pharmaceutica Sinica. B · 2019Review
- The role of dihydrosphingolipids in disease.Cellular and molecular life sciences : CMLS · 2019Review
- Functional and proteomic analysis of a full thickness filaggrin-deficient skin organoid model.Wellcome open research · 2019Article
- Review
- Cystic fibrosis: the conductance regulator, ceramides, and possible treatments.Journal of molecular medicine (Berlin, Germany) · 2017Article
- Elevated Fibroblast growth factor 21 (FGF21) in obese, insulin resistant states is normalised by the synthetic retinoid Fenretinide in mice.Scientific reports · 2017Article
- Tumour biology of obesity-related cancers: understanding the molecular concept for better diagnosis and treatment.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Fenretinide (FEN) is a synthetic retinoid that inhibits obesity and insulin resistance in high-fat diet (HFD)-fed mice and completely prevents 3T3-L1 pre-adipocyte differentiation. The aim of this study was to determine the mechanism(s) of FEN action in 3T3-L1 adipocytes and in mice. We used the 3T3-L1 model of adipogenesis, fully differentiated 3T3-L1 adipocytes and adipose tissue from HFD-induced obese mice to investigate the mechanisms of FEN action. We measured expression of adipogenic and retinoid genes by qPCR and activation of nutrient-signalling pathways by western blotting. Global lipid and metabolite analysis was performed and specific ceramide lipid species measured by liquid chromatography-mass spectrometry. We provide direct evidence that FEN inhibits 3T3-L1 adipogenesis via RA-receptor (RAR)-dependent signaling. However, RARα antagonism did not prevent FEN-induced decreases in lipid levels in mature 3T3-L1 adipocytes, suggesting an RAR-independent mechanism. Lipidomics analysis revealed that FEN increased dihydroceramide lipid species 5- to 16-fold in adipocytes, indicating an inhibition of the final step of ceramide biosynthesis. A similar blockade in adipose tissue from FEN-treated obese mice was associated with a complete normalisation of impaired mitochondrial β-oxidation and tricarboxylic acid cycle flux. The FEN catabolite, 4-oxo-N-(4-hydroxyphenyl)retinamide (4-OXO), also decreased lipid accumulation without affecting adipogenesis. FEN and 4-OXO (but not RA) treatment additionally led to the activation of p38-MAPK, peIF2α and autophagy markers in adipocytes. Overall our data reveals FEN utilises both RAR-dependent and -independent pathways to regulate adipocyte biology, both of which may be required for FEN to prevent obesity and insulin resistance in vivo.
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