ArticleScience advances2025
A long-term ketogenic diet causes hyperlipidemia, liver dysfunction, and glucose intolerance from impaired insulin secretion in mice.
Article in Science advances, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Ketogenic Diet Prevents Obesity-Associated Pancreatic Cancer Independent of Weight Loss and Induces Pancreatic Metabolic Reprogramming.Cancer research · 2026Article
- Article
- Ketogenic Diet in Obesity and Diabetes: A Narrative Review.Nutrients · 2026Review
- Treatment of Autosomal Dominant Polycystic Kidney Disease: Integrating Clinical Practice Guidelines, Patient Perspectives, and Real-World Effectiveness.Journal of the American Society of Nephrology : JASN · 2026Review
- In vivo assessment of the recovery of myocardial pyruvate dehydrogenase activity following a ketogenic diet.Cardiovascular research · 2026Article
- Effects of Diet Strategy and Nutrients on the Progression and Prevention of Diabetic Cardiomyopathy: A Narrative Review.Food science & nutrition · 2026Review
- Divergent Liver and Kidney Metabolic Responses to Ketogenic, High-Fat, and Sucrose-Enriched Diets in Mice.Nutrients · 2026Article
- Sex-Specific Metabolic Footprint of Ketogenic Diet in C57BL/6J Mice.Biomedicines · 2026Article
- The Diet-Multiple Sclerosis Connection: Oxidative Stress and Emerging Mechanisms.Molecular neurobiology · 2026Review
- Tryptophan and polyamine metabolism dysregulation serves as an early marker of high-fat diet-induced glucose intolerance.Journal of lipid research · 2026Article
- The Ketogenic Diet in Type 2 Diabetes and Obesity: A Narrative Review of Clinical Evidence.Nutrients · 2026Review
- Review
- Impacts of ketogenic diet intervention on cardiometabolic outcomes in obese, dysglycemic mice.Cardiovascular diabetology · 2026Review
- A narrative review of dietary patterns in cardiovascular-kidney-metabolic syndrome.Frontiers in nutrition · 2026Review
- Acetoacetate suppresses colon cancer via an MR1-MAIT axis.bioRxiv : the preprint server for biology · 2025Article
- Hyperlipidemia drives tumor growth in a mouse model of obesity-accelerated breast cancer growth.Cancer & metabolism · 2025Article
- The Neuroimmune Nexus: Diet-Induced Obesity, Inflammation, and Diet-Modulated Recovery Following Traumatic Brain Injury.Neurotrauma reportsReview
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Authors and funding
10 authors.
Funding
Abstract
Ketogenic diets (KDs)-very-low-carbohydrate and very-high-fat diets-have gained popularity as therapeutic against obesity and type 2 diabetes. However, their long-term effects on metabolic health remain understudied. Here, we show that, in male and female mice, a KD protects against weight gain and induces weight loss but over time leads to the development of hyperlipidemia, hepatic steatosis, and severe glucose intolerance. Unlike mice on conventional high-fat diet, KD-fed mice remain insulin sensitive and display low-insulin levels. Hyperglycemic clamp and ex vivo glucose-stimulated insulin secretion assays revealed systemic and cell-intrinsic impairments in insulin secretion. Transcriptomic profiling of islets from KD-fed mice indicated endoplasmic reticulum (ER)/Golgi stress and disrupted ER-Golgi protein trafficking, which were confirmed by electron microscopy showing a dilated Golgi network consistent with defective insulin granule trafficking and secretion. Together, these results suggest that long-term KD leads to multiple aberrations of metabolic parameters that caution their systematic use as a health-promoting dietary intervention.
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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 Socratic graph.