ArticleInternational journal of molecular sciences2021
Metformin Treatment Attenuates Brain Inflammation and Rescues PACAP/VIP Neuropeptide Alterations in Mice Fed a High-Fat Diet.
Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.
- Essential micronutrients and biguanides (metformin) synergistic and antagonistic interactions on neurocognitive outcomes in type two diabetes mellitus: a systematic review of preclinical and clinical evidence.Frontiers in endocrinology · 2026Pooled it
- Metabolic reprogramming is critical to microglial activation in Huntington's disease.JCI insight · 2026Article
- Metformin Induces Changes in Sphingosine-1-Phosphate-Related Signaling in Diabetic Mice Brain.International journal of molecular sciences · 2025Article
- Protective Effects of PACAP in Diabetic Complications: Retinopathy, Nephropathy and Neuropathy.International journal of molecular sciences · 2025Review
- PAC1 Receptor Knockout Mice Reveal Critical Links Between ER Stress, Myelin Homeostasis, and Neurodegeneration.International journal of molecular sciences · 2025Article
- Early Alterations of PACAP and VIP Expression in the Female Rat Brain Following Spinal Cord Injury.Journal of molecular neuroscience : MN · 2023Article
- Altered Hippocampal and Striatal Expression of Endothelial Markers and VIP/PACAP Neuropeptides in a Mouse Model of Systemic Lupus Erythematosus.International journal of molecular sciences · 2023Article
- [Metformin use and risk of ischemic stroke in patients with type 2 diabetes: A cohort study].Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences · 2023Article
- The function, mechanisms, and clinical applications of metformin: potential drug, unlimited potentials.Archives of pharmacal research · 2023Review
- Feeding the Brain: Effect of Nutrients on Cognition, Synaptic Function, and AMPA Receptors.Nutrients · 2022Review
- Dried Bilberry (International journal of molecular sciences · 2022Article
- Exploring the Pro-Phagocytic and Anti-Inflammatory Functions of PACAP and VIP in Microglia: Implications for Multiple Sclerosis.International journal of molecular sciences · 2022Review
- Quo Vadis Anesthesiologist? The Value Proposition of Future Anesthesiologists Lies in Preserving or Restoring Presurgical Health after Surgical Insult.Journal of clinical medicine · 2022Article
- The Anxiolytic Drug Buspirone Prevents Rotenone-Induced Toxicity in a Mouse Model of Parkinson's Disease.International journal of molecular sciences · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
High-fat diet (HFD)-induced comorbid cognitive and behavioural impairments are thought to be the result of persistent low-grade neuroinflammation. Metformin, a first-line medication for the treatment of type-2 diabetes, seems to ameliorate these comorbidities, but the underlying mechanism(s) are not clear. Pituitary adenylate cyclase-activating peptide (PACAP) and vasoactive intestinal peptide (VIP) are neuroprotective peptides endowed with anti-inflammatory properties. Alterations to the PACAP/VIP system could be pivotal during the development of HFD-induced neuroinflammation. To unveil the pathogenic mechanisms underlying HFD-induced neuroinflammation and assess metformin's therapeutic activities, (1) we determined if HFD-induced proinflammatory activity was present in vulnerable brain regions associated with the development of comorbid behaviors, (2) investigated if the PACAP/VIP system is altered by HFD, and (3) assessed if metformin rescues such diet-induced neurochemical alterations. C57BL/6J male mice were divided into two groups to receive either standard chow (SC) or HFD for 16 weeks. A further HFD group received metformin (HFD + M) (300 mg/kg BW daily for 5 weeks) via oral gavage. Body weight, fasting glucose, and insulin levels were measured. After 16 weeks, the proinflammatory profile, glial activation markers, and changes within the PI3K/AKT intracellular pathway and the PACAP/VIP system were evaluated by real-time qPCR and/or Western blot in the hypothalamus, hippocampus, prefrontal cortex, and amygdala. Our data showed that HFD causes widespread low-grade neuroinflammation and gliosis, with regional-specific differences across brain regions. HFD also diminished phospho-AKT
Indexed as
Identifiers
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.