ArticleThe Journal of biological chemistry2013
Neuronal Sirt1 deficiency increases insulin sensitivity in both brain and peripheral tissues.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 59 citations in OpenAlex.
- Article
- Review
- SIRT1 in forebrain excitatory neurons produces sexually dimorphic effects on depression-related behaviors and modulates neuronal excitability and synaptic transmission in the medial prefrontal cortex.Molecular psychiatry · 2020Article
- Overexpression of Sirtuin 1 protein in neurons prevents and reverses experimental diabetic neuropathy.Brain : a journal of neurology · 2019Article
- Caffeic Acid Phenethyl Ester (CAPE) Protects PC12 Cells Against Cisplatin-Induced Neurotoxicity by Activating the AMPK/SIRT1, MAPK/Erk, and PI3k/Akt Signaling Pathways.Neurotoxicity research · 2019Article
- SIRT1 in Astrocytes Regulates Glucose Metabolism and Reproductive Function.Endocrinology · 2019Article
- Neuronal SIRT1 Regulates Metabolic and Reproductive Function and the Response to Caloric Restriction.Journal of the Endocrine Society · 2019Article
- Molecular and Environmental Mechanisms Regulating Puberty Initiation: An Integrated Approach.Frontiers in endocrinology · 2019Review
- Understanding the Role of Dysfunctional and Healthy Mitochondria in Stroke Pathology and Its Treatment.International journal of molecular sciences · 2018Review
- Distinctive Roles of Sirtuins on Diabetes, Protective or Detrimental?Frontiers in endocrinology · 2018Review
- Brain SIRT1 Mediates Metabolic Homeostasis and Neuroprotection.Frontiers in endocrinology · 2018Review
- Temporal overexpression of SIRT1 in skeletal muscle of adult mice does not improve insulin sensitivity or markers of mitochondrial biogenesis.Acta physiologica (Oxford, England) · 2017Article
- In Search of New Therapeutic Targets in Obesity Treatment: Sirtuins.International journal of molecular sciences · 2016Review
- The Nutrient and Energy Sensor Sirt1 Regulates the Hypothalamic-Pituitary-Adrenal (HPA) Axis by Altering the Production of the Prohormone Convertase 2 (PC2) Essential in the Maturation of Corticotropin-releasing Hormone (CRH) from Its Prohormone in Male Rats.The Journal of biological chemistry · 2016Article
- Brain signaling systems in the Type 2 diabetes and metabolic syndrome: promising target to treat and prevent these diseases.Future science OA · 2015Review
- FGF21 does not require interscapular brown adipose tissue and improves liver metabolic profile in animal models of obesity and insulin-resistance.Scientific reports · 2015Article
- Adipocyte SIRT1 knockout promotes PPARγ activity, adipogenesis and insulin sensitivity in chronic-HFD and obesity.Molecular metabolism · 2015Article
- Sirtuins in epigenetic regulation.Chemical reviews · 2015Review
- Central Sirt1 regulates body weight and energy expenditure along with the POMC-derived peptide α-MSH and the processing enzyme CPE production in diet-induced obese male rats.Endocrinology · 2015Article
- The promise and perils of HDAC inhibitors in neurodegeneration.Annals of clinical and translational neurology · 2015Review
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 1 country.
Funding
Abstract
Sirt1 is a NAD(+)-dependent class III deacetylase that functions as a cellular energy sensor. In addition to its well-characterized effects in peripheral tissues, emerging evidence suggests that neuronal Sirt1 activity plays a role in the central regulation of energy balance and glucose metabolism. To assess this idea, we generated Sirt1 neuron-specific knockout (SINKO) mice. On both standard chow and HFD, SINKO mice were more insulin sensitive than Sirt1(f/f) mice. Thus, SINKO mice had lower fasting insulin levels, improved glucose tolerance and insulin tolerance, and enhanced systemic insulin sensitivity during hyperinsulinemic euglycemic clamp studies. Hypothalamic insulin sensitivity of SINKO mice was also increased over controls, as assessed by hypothalamic activation of PI3K, phosphorylation of Akt and FoxO1 following systemic insulin injection. Intracerebroventricular injection of insulin led to a greater systemic effect to improve glucose tolerance and insulin sensitivity in SINKO mice compared with controls. In line with the in vivo results, insulin-induced AKT and FoxO1 phosphorylation were potentiated by inhibition of Sirt1 in a cultured hypothalamic cell line. Mechanistically, this effect was traced to a reduced effect of Sirt1 to directly deacetylate and repress IRS-1 function. The enhanced central insulin signaling in SINKO mice was accompanied by increased insulin receptor signal transduction in liver, muscle, and adipose tissue. In summary, we conclude that neuronal Sirt1 negatively regulates hypothalamic insulin signaling, leading to systemic insulin resistance. Interventions that reduce neuronal Sirt1 activity have the potential to improve systemic insulin action and limit weight gain on an obesigenic diet.
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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.