ArticleJournal of the American Heart Association2021
Modulation of Sirt1 and FoxO1 on Hypothalamic Leptin-Mediated Sympathetic Activation and Inflammation in Diet-Induced Obese Rats.
Article in Journal of the American Heart Association, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 25 citations in OpenAlex.
- Article
- Harnessing the FOXO-SIRT1 axis: insights into cellular stress, metabolism, and aging.Biogerontology · 2025Review
- Update on Hypothalamic Inflammation and Gliosis: Expanding Evidence of Relevance Beyond Obesity.Current obesity reports · 2025Review
- The New Challenge of Obesity - Obesity-Associated Nephropathy.Diabetes, metabolic syndrome and obesity : targets and therapy · 2024Review
- Impact of Chronic Intermittent Hypoxia on Cognitive Function and Hippocampal Neurons in Mice: A Study of Inflammatory and Oxidative Stress Pathways.Nature and science of sleep · 2024Article
- HFD-exacerbated Metabolic Side Effects of Olanzapine Are Suppressed by ER Stress Inhibitor.Current medical science · 2023Article
- Changes of Signaling Pathways in Hypothalamic Neurons with Aging.Current issues in molecular biology · 2023Review
- Review
- Resveratrol Improves the Progression of Osteoarthritis by Regulating the SIRT1-FoxO1 Pathway-Mediated Cholesterol Metabolism.Mediators of inflammation · 2023Article
- Resveratrol in the Hypothalamic Paraventricular Nucleus Attenuates Hypertension by Regulation of ROS and Neurotransmitters.Nutrients · 2022Article
- Resveratrol protection against IL-1β-induced chondrocyte damage via the SIRT1/FOXO1 signaling pathway.Journal of orthopaedic surgery and research · 2022Article
- Review
- Hypothalamic inflammation in metabolic disorders and aging.Cellular and molecular life sciences : CMLS · 2021Review
- Modulation of Sirt1 and FoxO1 on Hypothalamic Leptin-Mediated Sympathetic Activation and Inflammation in Diet-Induced Obese Rats.Journal of the American Heart Association · 2021Article
- C1q/TNF-related protein-1: Potential biomarker for early diagnosis of autism spectrum disorder.International journal of immunopathology and pharmacologyArticle
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background Hypothalamic leptin-mediated signaling contributes to the exaggerated sympatho-excitation and increased blood pressure in obesity-associated hypertension. The aim of the study was to investigate the roles of energy-sensing enzyme sirtuin1 (Sirt1) and forkhead box protein O1 (FoxO1) on the hypothalamic leptin-mediated high sympathetic nerve activity and inflammation in obesity. Methods and Results Sprague Dawley rats were fed with high-fat diet (HFD) for 12 weeks. In vivo, the potential of Srit1 and FoxO1 in the sympathetic effects of leptin was investigated via siRNA injection to knockdown Sirt1 or FoxO1 gene in the arcuate nucleus (ARCN) of hypothalamus in rats. In vitro, the effects of Sirt1 or FoxO1 on leptin-mediated inflammation were observed in proopiomelanocortin (POMC) and microglial cells. Knockdown Sirt1 by siRNA significantly reduced the renal sympathetic nerve activity (RSNA) and blood pressure responses to leptin injection in the ARCN in the HFD rats. Conversely, knockdown FoxO1 significantly enhanced the RSNA and blood pressure responses to leptin injection in the HFD rats. Knockdown Sirt1 reduced the levels of pro-inflammatory cytokines interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), C1q/TNF-related protein-1 (CTRP1), and immune cell infiltration in the ARCN in the HFD rats. Knockdown FoxO1 significantly increased the level of IL-6 in the ARCN of HFD rats. In cultured hypothalamic POMC and microglial cells, knockdown Sirt1 significantly reduced leptin-induced IL-6 expression, affected the levels of AMP-activated protein kinase (AMPK) and serine/threonine-specific protein kinase (Akt). Knockdown FoxO1 significantly increased leptin-induced IL-6 in both POMC cells and microglial cells. Conclusions These data suggest that both Sirt1 and FoxO1 are the key modulators of leptin signaling in the hypothalamus contributed to the over sympathetic activation and inflammation in obesity.
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