ArticleAmerican journal of physiology. Endocrinology and metabolism2017
Long-term high-fat diet induces hippocampal microvascular insulin resistance and cognitive dysfunction.
Article in American journal of physiology. Endocrinology and metabolism, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 76 citations in OpenAlex.
- Mediterranean and Western diet effects on Alzheimer's disease biomarkers, cerebral perfusion, and cognition in mid-life: A randomized trial.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2022Trial
- Effects of obesity on brain health and cognition.Nature reviews. Neurology · 2026Review
- Capillary-Associated Microglia in Neurovascular Coupling: Localization, Mechanisms, and Disease Implications.Journal of neuroinflammation · 2026Review
- Bioenergetics and lipid metabolism in Alzheimer's disease: From cell biology to systemic health.Journal of internal medicine · 2026Review
- The triglyceride-glucose index for diabetic retinopathy prediction in Chinese patients with type 2 diabetes: a preliminary cross-sectional study.Frontiers in endocrinology · 2026Article
- Astrocytes of the hippocampus and responses to periprandial neuroendocrine hormones.Physiology & behavior · 2025Review
- Risk Factors, Pathological Changes, and Potential Treatment of Diabetes-Associated Cognitive Dysfunction.Journal of diabetes · 2025Review
- Nutrigenomic influence of a curcumin-supplemented high glycemic diet on hippocampal microvasculature in male C57BL/6J mice.Frontiers in nutrition · 2025Article
- An acute bout of resistance exercise increases BDNF in hippocampus and restores the long-term memory of insulin-resistant rats.Experimental brain research · 2024Article
- Effects of Modified Dietary Fiber from Fresh Corn Bracts on Obesity and Intestinal Microbiota in High-Fat-Diet Mice.Molecules (Basel, Switzerland) · 2023Article
- The Role of Oxidative Stress and Inflammation in Obesity and Its Impact on Cognitive Impairments-A Narrative Review.Antioxidants (Basel, Switzerland) · 2023Review
- Dimethyl itaconate ameliorates cognitive impairment induced by a high-fat diet via the gut-brain axis in mice.Microbiome · 2023Article
- Effects of different diets used to induce obesity/metabolic syndrome on bladder function in rats.American journal of physiology. Regulatory, integrative and comparative physiology · 2023Article
- The Obesity Paradox: Effect of Body Mass Index and Waist Circumference on Post-Stroke Cognitive Impairment.Diabetes, metabolic syndrome and obesity : targets and therapy · 2023Article
- Dysmetabolism and Neurodegeneration: Trick or Treat?Nutrients · 2022Review
- The Effect of Dietary Fat and Sucrose on Cognitive Functioning in Mice Lacking Insulin Signaling in Neuropeptide Y Neurons.Frontiers in physiology · 2022Article
- Memory and eating: A bidirectional relationship implicated in obesity.Neuroscience and biobehavioral reviews · 2022Review
- Diabetes pathogenesis and management: the endothelium comes of age.Journal of molecular cell biology · 2021Article
- Obesity-induced cognitive impairment in older adults: a microvascular perspective.American journal of physiology. Heart and circulatory physiology · 2021Article
- Capillary Rarefaction in Obesity and Metabolic Diseases-Organ-Specificity and Possible Mechanisms.Cells · 2020Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Insulin action on hippocampus improves cognitive function, and obesity and type 2 diabetes are associated with decreased cognitive function. Cerebral microvasculature plays a critical role in maintaining cerebral vitality and function by supplying nutrients, oxygen, and hormones such as insulin to cerebral parenchyma, including hippocampus. In skeletal muscle, insulin actively regulates microvascular opening and closure, and this action is impaired in the insulin-resistant states. To examine insulin's action on hippocampal microvasculature and parenchyma and the impact of diet-induced obesity, we determined cognitive function and microvascular insulin responses, parenchyma insulin responses, and capillary density in the hippocampus in 2- and 8-mo-old rats on chow diet and 8-mo-old rats on a long-term high-fat diet (6 mo). Insulin infusion increased hippocampal microvascular perfusion in rats on chow diet by ~80-90%. High-fat diet feeding completely abolished insulin-mediated microvascular responses and protein kinase B phosphorylation but did not alter the capillary density in the hippocampus. This was associated with a significantly decreased cognitive function assessed using both the two-trial spontaneous alternation behavior test and the novel object recognition test. As the microvasculature provides the needed endothelial surface area for delivery of nutrients, oxygen, and insulin to hippocampal parenchyma, we conclude that hippocampal microvascular insulin resistance may play a critical role in the development of cognitive impairment seen in obesity and diabetes. Our results suggest that improvement in hippocampal microvascular insulin sensitivity might help improve or reverse cognitive function in the insulin-resistant states.
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Registered trials
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