ArticleProceedings of the National Academy of Sciences of the United States of America2018
High salt intake causes leptin resistance and obesity in mice by stimulating endogenous fructose production and metabolism.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 166 papers, 3 of them syntheses that pooled it.
What it found
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
166 citing papers in PubMed, 3 syntheses or guidelines pooled it, 275 citations in OpenAlex.
- Acute Intake of Fructose Increases Arterial Pressure in Humans: A Meta-Analysis and Systematic Review.Nutrients · 2024Pooled it
- Ultra-Processed Food Consumption and Adult Diabetes Risk: A Systematic Review and Dose-Response Meta-Analysis.Nutrients · 2021Pooled it
- Sodium status is associated with type 2 diabetes mellitus: a systematic review and meta-analysis of observational studies.European journal of nutrition · 2021Pooled it
- Gene-environment interaction modifies the association between hyperinsulinemia and serum urate levels through SLC22A12.The Journal of clinical investigation · 2025Trial
- The impact of dietary sodium and fructose on renal sodium handling and blood pressure in healthy adults.Physiological reports · 2025Trial
- Urinary Sodium Excretion and Salt Intake Are Not Associated With Blood Pressure Variability in a White General Population.Journal of the American Heart Association · 2023Trial
- Influence of Dietary Salt Intake on T2D Treatment.Frontiers in endocrinology · 2022Trial
- Role of skeletal muscle perfusion and insulin resistance in the effect of dietary sodium on heart function in overweight.ESC heart failure · 2021Trial
- Acute effects of salt on blood pressure are mediated by serum osmolality.Journal of clinical hypertension (Greenwich, Conn.) · 2018Trial
- Dietary sodium density as a potential nutritional marker of HSI-defined hepatic steatosis in Korean adults: a nationwide cross-sectional study with a dose-response analysis.Internal and emergency medicine · 2026Article
- Integrated morphological and transcriptomic analysis of bone disorders in aldosterone-salt hypertension.Hypertension research : official journal of the Japanese Society of Hypertension · 2026Article
- Dehydration promotes intracellular lipid synthesis and accumulation.Nature communications · 2026Article
- Fructose: metabolic signal and modern hazard.Nature metabolism · 2026Review
- A brain-specific microRNA,Genes & development · 2026Article
- Dietary Sodium Intake and Risk of Incident Heart Failure in the Southern Community Cohort Study.JACC. Advances · 2026Article
- Association Between Salt Intake and Body Adiposity in Chinese Population: A Repeated-Measures Cohort Study.Nutrients · 2026Observational
- Comparative physiology and biomimetics in metabolic and environmental health: what can we learn from extreme animal phenotypes?Diabetologia · 2026Review
- High Estimated 24-Hour Urinary Sodium Excretion is Associated With Metabolic Syndrome and Its Phenotypes: Tehran Lipid and Glucose Study.Journal of nutrition and metabolism · 2026Article
- New Insight Into Male Infertility: Deviation From Basic Tenets of Life.Oxidative medicine and cellular longevity · 2026Review
- High salt intake and its dual impact on obesity and cardiovascular mortality in individuals over 50: a paradoxical relationship.BMC public health · 2025Article
106 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
Dietary guidelines for obesity typically focus on three food groups (carbohydrates, fat, and protein) and caloric restriction. Intake of noncaloric nutrients, such as salt, are rarely discussed. However, recently high salt intake has been reported to predict the development of obesity and insulin resistance. The mechanism for this effect is unknown. Here we show that high intake of salt activates the aldose reductase-fructokinase pathway in the liver and hypothalamus, leading to endogenous fructose production with the development of leptin resistance and hyperphagia that cause obesity, insulin resistance, and fatty liver. A high-salt diet was also found to predict the development of diabetes and nonalcoholic fatty liver disease in a healthy population. These studies provide insights into the pathogenesis of obesity and diabetes and raise the potential for reduction in salt intake as an additional interventional approach for reducing the risk for developing obesity and metabolic syndrome.
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What OpenQuestion holds
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.