SIRT6 is a member of a highly conserved family of NAD(+)-dependent deacetylases with various roles in metabolism, stress resistance, and life span. SIRT6-deficient mice develop normally but succumb to a lethal hypoglycemia early in life; however, the mechanism underlying this hypoglycemia remained unclear. Here, we demonstrate that SIRT6 functions as a histone H3K9 deacetylase to control the expression of multiple glycolytic genes. Specifically, SIRT6 appears to function as a corepressor of the transcription factor Hif1alpha, a critical regulator of nutrient stress responses. Consistent with this notion, SIRT6-deficient cells exhibit increased Hif1alpha activity and show increased glucose uptake with upregulation of glycolysis and diminished mitochondrial respiration. Our studies uncover a role for the chromatin factor SIRT6 as a master regulator of glucose homeostasis and may provide the basis for novel therapeutic approaches against metabolic diseases, such as diabetes and obesity.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2821045 | PMC |
| http://dx.doi.org/10.1016/j.cell.2009.12.041 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Type 3 deiodinase activation mediated by the Shh/Gli1 axis promotes sepsis-induced metabolic dysregulation in skeletal muscles.
Burns Trauma
January 2025
Department of Critical Care Medicine, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, No. 321 Zhongshan Road, Gulou District, Nanjing, Jiangsu 210008, China.
Background: Non-thyroidal illness syndrome is commonly observed in critically ill patients, characterized by the inactivation of systemic thyroid hormones (TH), which aggravates metabolic dysfunction. Recent evidence indicates that enhanced TH inactivation is mediated by the reactivation of type 3 deiodinase (Dio3) at the tissue level, culminating in a perturbed local metabolic equilibrium. This study assessed whether targeted inhibition of Dio3 can maintain tissue metabolic homeostasis under septic conditions and explored the mechanism behind Dio3 reactivation.
View Article and Find Full Text PDFSelf-healable and pH-responsive spermidine/ferrous ion complexed hydrogel Co-loaded with CA inhibitor and glucose oxidase for combined cancer immunotherapy through triple ferroptosis mechanism.
Bioact Mater
May 2025
Bioscience and Biomedical Engineering Thrust, The Hong Kong University of Science and Technology (Guangzhou), Guangzhou, 511400, China.
Tumor microenvironment governs various therapeutic tolerability of cancer such as ferroptosis and immunotherapy through rewiring tumor metabolic reprogramming like Warburg metabolism. Highly expressed carbonic anhydrases (CA) in tumor that maintaining the delicate metabolic homeostasis is thus the most potential target to be modulated to resolve the therapeutic tolerability. Hence, in this article, a self-healable and pH-responsive spermidine/ferrous ion hydrogel loaded with CA inhibitor (acetazolamide, ACZ) and glucose oxidase (ACZ/GOx@SPM-HA Gel) was fabricated through the Schiff-base reaction between spermidine-dextran and oxidized hyaluronic acid, along with ferrous coordination.
View Article and Find Full Text PDFAn inter-organ neuro-immuno-endocrine circuit for glucose homeostasis.
Nat Rev Immunol
January 2025
Nature Reviews Immunology, .
The E3-ligase Siah2 activates mitochondrial quality control in neurons to maintain energy metabolism during ischemic brain tolerance.
Cell Death Dis
January 2025
Division of Pharmacology, Department of Neuroscience, School of Medicine, University of Naples "Federico II", Naples, Italy.
Mitochondrial quality control is crucial for the homeostasis of the mitochondrial network. The balance between mitophagy and biogenesis is needed to reduce cerebral ischemia-induced cell death. Ischemic preconditioning (IPC) represents an adaptation mechanism of CNS that increases tolerance to lethal cerebral ischemia.
View Article and Find Full Text PDFGlucose Metabolic Abnormalities and Their Interaction With Defective Phosphate Homeostasis in Tumor-induced Osteomalacia.
J Clin Endocrinol Metab
January 2025
Department of Endocrinology, Key Laboratory of Endocrinology, State Key Laboratory of Complex Severe and Rare Diseases, Dongcheng District, National Commission of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China.
Context: Phosphate homeostasis was compromised in tumor-induced osteomalacia (TIO) due to increased fibroblast growth factor 23 (FGF23) secretion. Nevertheless, the glucose metabolic profile in TIO patients has not been investigated.
Objectives: This work aimed to clarify the glucose metabolic profiles in TIO patients and explore their interaction with impaired phosphate homeostasis.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!