ArticlePloS one2015
High-fat diet induces hepatic insulin resistance and impairment of synaptic plasticity.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 128 papers, 1 of them a synthesis that pooled it.
What it found
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Who cites it
128 citing papers in PubMed, 1 synthesis or guideline pooled it, 228 citations in OpenAlex.
- Berry Consumption and Its Role in the Modulation of Obesity and Mild Cognitive Impairment.Nutrients · 2026Pooled it
- High‑fat diet exacerbates hepatic and adipose insulin signaling impairment and ovarian lesions in a rat model of letrozole‑induced polycystic ovary syndrome.Molecular medicine reports · 2026Article
- Liver androgen receptor knockout protects female mice from high fat diet-induced insulin resistance.npj metabolic health and disease · 2026Article
- Kisspeptin-10 Alleviates Obesity-induced Testicular Oxidative Stress and Mitochondrial Dysfunction via Modulation of Mitophagy and Autophagy Signaling.Reproductive sciences (Thousand Oaks, Calif.) · 2026Article
- Loss of the calorie restriction response protein DEPP1 worsens diet-induced obesity.Endocrinology · 2026Article
- Article
- APOE-ε4 genotype and western diet synergistically aggravate synaptic dysfunction in Alzheimer's disease via D-serine disruption.Alzheimer's research & therapy · 2026Article
- Effect of an oat cookie enriched with bean flour biotransformed byFrontiers in nutrition · 2026Article
- Impact of Combination Therapy With Caffeine and Naringin on Insulin Resistance and Renal Function in a Nonalcoholic Fatty Liver Disease Rat Model.BioMed research international · 2026Article
- Article
- The role of enteroendocrine cells, hormones, and gut microbiota in anorexia nervosa: a complex interplay of the microbiome-gut-brain axis.Molecular biology reports · 2025Review
- Protective effects of Parabacteroides distasonis against high-fat diet-induced brain injury in mice.NPJ science of food · 2025Article
- Breaking the metabolic-inflammatory vicious cycle in polycystic ovary syndrome: a comparative review of ketogenic and high-fat diets.Lipids in health and disease · 2025Review
- Acute high glucose exposure impairs synaptosomal vesicle release activity.Brain research · 2025Article
- Insulin resistance alters cortical inhibitory neurons and microglia to exacerbate Alzheimer's knock-in mouse phenotypes.bioRxiv : the preprint server for biology · 2025Article
- Blood-Brain Barrier Integrity and Transport of Major Hormones are Unchanged in Mice With Euglycemic Hyperinsulinemia.Endocrinology · 2025Article
- Lipids dysregulation in diseases: core concepts, targets and treatment strategies.Lipids in health and disease · 2025Review
- Melanocortin 3 receptor regulates hepatic autophagy and systemic adiposity.Nature communications · 2025Article
- Crosstalk between MSC-extracellular vesicles andFrontiers in pharmacology · 2025Article
- Pathology and Treatments of Alzheimer's Disease Based on Considering Changes in Brain Energy Metabolism Due to Type 2 Diabetes.Molecules (Basel, Switzerland) · 2024Review
68 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
High-fat diet (HFD)-induced obesity is associated with insulin resistance, which may affect brain synaptic plasticity through impairment of insulin-sensitive processes underlying neuronal survival, learning, and memory. The experimental model consisted of 3 month-old C57BL/6J mice fed either a normal chow diet (control group) or a HFD (60% of calorie from fat; HFD group) for 12 weeks. This model was characterized as a function of time in terms of body weight, fasting blood glucose and insulin levels, HOMA-IR values, and plasma triglycerides. IRS-1/Akt pathway was assessed in primary hepatocytes and brain homogenates. The effect of HFD in brain was assessed by electrophysiology, input/output responses and long-term potentiation. HFD-fed mice exhibited a significant increase in body weight, higher fasting glucose- and insulin levels in plasma, lower glucose tolerance, and higher HOMA-IR values. In liver, HFD elicited (a) a significant decrease of insulin receptor substrate (IRS-1) phosphorylation on Tyr608 and increase of Ser307 phosphorylation, indicative of IRS-1 inactivation; (b) these changes were accompanied by inflammatory responses in terms of increases in the expression of NFκB and iNOS and activation of the MAP kinases p38 and JNK; (c) primary hepatocytes from mice fed a HFD showed decreased cellular oxygen consumption rates (indicative of mitochondrial functional impairment); this can be ascribed partly to a decreased expression of PGC1α and mitochondrial biogenesis. In brain, HFD feeding elicited (a) an inactivation of the IRS-1 and, consequentially, (b) a decreased expression and plasma membrane localization of the insulin-sensitive neuronal glucose transporters GLUT3/GLUT4; (c) a suppression of the ERK/CREB pathway, and (d) a substantial decrease in long-term potentiation in the CA1 region of hippocampus (indicative of impaired synaptic plasticity). It may be surmised that 12 weeks fed with HFD induce a systemic insulin resistance that impacts profoundly on brain activity, i.e., synaptic plasticity.
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What Socratic 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 Socratic graph.