ArticleCell death discovery2021
Metformin attenuates hypothalamic inflammation via downregulation of RIPK1-independent microglial necroptosis in diet-induced obese mice.
Article in Cell death discovery, 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
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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.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 17 citations in OpenAlex.
- Effects of diabetes on microglial physiology: a systematic review of in vitro, preclinical and clinical studies.Journal of neuroinflammation · 2023Pooled it
- Autophagy in hypothalamic POMC and AgRP neurons: mechanisms and therapeutic implications for obesity.International journal of obesity (2005) · 2026Review
- The critical role of necroptosis in oil cyst formation associated with autologous fat transplantation.Cell communication and signaling : CCS · 2026Article
- TNF as a mediator of metabolic inflammation and body-brain interaction in obesity-driven neuroinflammation and neurodegeneration.Ageing research reviews · 2025Review
- Metabolic inflammatory hypothalamic-induced reproductive dysfunction: a new paradigm in adolescent reproductive-endocrine health.World journal of pediatrics : WJP · 2025Article
- Metabolic syndrome: molecular mechanisms and therapeutic interventions.Molecular biomedicine · 2025Review
- Advances in the Study of Necroptosis in Vascular Dementia: Focus on Blood-Brain Barrier and Neuroinflammation.CNS neuroscience & therapeutics · 2025Review
- Necroptosis in obesity: a complex cell death event.Apoptosis : an international journal on programmed cell death · 2025Review
- Superior metabolic improvement of polycystic ovary syndrome traits after GLP1-based multi-agonist therapy.Nature communications · 2024Article
- Article
- Metformin inhibits inflammatory response and endoplasmic reticulum stress to improve hypothalamic aging in obese mice.iScience · 2023Article
- HSP70 attenuates neuronal necroptosis through the HSP90α-RIPK3 pathway following neuronal trauma.Molecular biology reports · 2023Article
- The function, mechanisms, and clinical applications of metformin: potential drug, unlimited potentials.Archives of pharmacal research · 2023Review
- The role of hypothalamic endoplasmic reticulum stress in schizophrenia and antipsychotic-induced weight gain: A narrative review.Frontiers in neuroscience · 2022Review
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 1 country.
Funding
Abstract
Necroptosis, a form of programmed cell death, accounts for many inflammations in a wide range of diseases. Diet-induced obesity is manifested by low-grade inflammation in the mediobasal hypothalamus (MBH), and microglia are implicated as critical responsive components for this process. Here, we demonstrate that microglial necroptosis plays a pivotal role in obesity-related hypothalamic inflammation, facilitating proinflammatory cytokine production, such as TNF-α and IL-1β. Treatment with the anti-diabetic drug metformin effectively reduces the obese phenotypes in the high-fat diet (HFD)-fed mice, attributing to remission of hypothalamic inflammation partly through repressing microglial necroptosis. Importantly, using the receptor-interacting protein kinase 1 inhibitor, necrostatin-1s, could not suppress the microglial inflammation nor prevent body weight gain in the obese mice, indicating that the microglial necroptosis is RIPK1-independent. Altogether, these findings offer new insights into hypothalamic inflammation in diet-induced obesity and provide a novel mechanism of action for metformin in obesity treatment.
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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.