ArticleAmerican journal of physiology. Endocrinology and metabolism2009
Long-term Fenretinide treatment prevents high-fat diet-induced obesity, insulin resistance, and hepatic steatosis.
Article in American journal of physiology. Endocrinology and metabolism, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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Who cites it
70 citing papers in PubMed, 105 citations in OpenAlex.
- Key Hepatokines Linking MASLD and Type 2 Diabetes: From Pathophysiological Mechanisms to Therapeutic Modulation.International journal of molecular sciences · 2026Review
- Inhibition of ceramide synthesis ameliorates body wasting in a cancer cachexia model.The Journal of clinical investigation · 2026Article
- Genetic underpinnings of type-2 diabetes (T2D) with colorectal cancer (CRC): In-silico discovery of common molecular signatures, pathogenetic processes and therapeutic candidates.Journal, genetic engineering & biotechnology · 2026Article
- Effects of Diet and Exercise on Mitochondrial Health in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): Role of Ceramides.Nutrients · 2025Review
- Transporters in vitamin uptake and cellular metabolism: impacts on health and disease.Life metabolism · 2025Review
- A New Strategy for Obesity Treatment: Revealing the Frontiers of Anti-obesity Medications.Current molecular medicine · 2025Review
- Immunometabolic effects ofImmunometabolism (Cobham, Surrey) · 2024Review
- Retinol binding protein 4 and type 2 diabetes: from insulin resistance to pancreatic β-cell function.Endocrine · 2024Review
- Ceramides are fuel gauges on the drive to cardiometabolic disease.Physiological reviews · 2024Review
- Attempts to Improve Lipophilic Drugs' Solubility and Bioavailability: A Focus on Fenretinide.Pharmaceutics · 2024Review
- Article
- Fenretinide inhibits obesity and fatty liver disease but induces Smpd3 to increase serum ceramides and worsen atherosclerosis in LDLRScientific reports · 2023Article
- Targeting macrophagic 17Acta pharmaceutica Sinica. B · 2023Article
- Pretreatment of human retinal pigment epithelial cells with sterculic acid forestalls fenretinide-induced apoptosis.Scientific reports · 2022Article
- Interplay of retinol binding protein 4 with obesity and associated chronic alterations (Review).Molecular medicine reports · 2022Review
- Retinoid Homeostasis and Beyond: How Retinol Binding Protein 4 Contributes to Health and Disease.Nutrients · 2022Review
- Fenretinide Reduces Intestinal Mucin-2-Positive Goblet Cells in Chronic Alcohol Abuse.Pharmacology · 2022Article
- Ceramides and other sphingolipids as drivers of cardiovascular disease.Nature reviews. Cardiology · 2021Review
- Bioactive Sphingolipids as Major Regulators of Coronary Artery Disease.Biomolecules & therapeutics · 2021Review
- Roles of Ceramides in Non-Alcoholic Fatty Liver Disease.Journal of clinical medicine · 2021Review
10 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The synthetic retinoid Fenretinide (FEN) increases insulin sensitivity in obese rodents and is in early clinical trials for treatment of insulin resistance in obese humans with hepatic steatosis (46). We aimed to determine the physiological mechanisms for the insulin-sensitizing effects of FEN. Wild-type mice were fed a high-fat diet (HFD) with or without FEN from 4-5 wk to 36-37 wk of age (preventive study) or following 22 wk of HF diet-induced obesity (12 wk intervention study). Retinol-binding protein-4 (RBP4) knockout mice were also fed the HFD with or without FEN in a preventive study. FEN had minimal effects on HFD-induced body weight gain but markedly reduced HFD-induced adiposity and hyperleptinemia in both studies. FEN-HFD mice gained epididymal fat but not subcutaneous or visceral fat mass in contrast to HFD mice without FEN. FEN did not have a measurable effect on energy expenditure, food intake, physical activity, or stool lipid content. Glucose infusion rate during hyperinsulinemic-euglycemic clamp was reduced 86% in HFD mice compared with controls and was improved 3.6-fold in FEN-HFD compared with HFD mice. FEN improved insulin action on glucose uptake and glycogen levels in muscle, insulin-stimulated suppression of hepatic glucose production, and suppression of serum FFA levels in HFD mice. Remarkably, FEN also reduced hepatic steatosis. In RBP4 knockout mice, FEN reduced the HFD-induced increase in adiposity and hyperleptinemia. In conclusion, long-term therapy with FEN partially prevents or reverses obesity, insulin resistance, and hepatic steatosis in mice on HFD. The anti-adiposity effects are independent of the RBP4 lowering effect.
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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.