Programming and Regulation of Metabolic Homeostasis by HDAC11
Histone deacetylases (HDACs) are enzymes that regulate protein functions by catalyzing the removal of acetyl and acyl groups from lysine residues. They play pivotal roles in governing cell behaviors and are indispensable in numerous biological processes. HDAC11, the last identified and sole member o...
| Hoofdauteurs: | , , , , , , |
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| Formaat: | Artikel |
| Taal: | English |
| Gepubliceerd in: |
Elsevier
2018-07-01
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| Reeks: | EBioMedicine |
| Online toegang: | http://www.sciencedirect.com/science/article/pii/S2352396418302317 |
| _version_ | 1828861580463308800 |
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| author | Lei Sun Caralina Marin de Evsikova Ka Bian Alexandra Achille Elphine Telles Huadong Pei Edward Seto |
| author_facet | Lei Sun Caralina Marin de Evsikova Ka Bian Alexandra Achille Elphine Telles Huadong Pei Edward Seto |
| author_sort | Lei Sun |
| collection | DOAJ |
| description | Histone deacetylases (HDACs) are enzymes that regulate protein functions by catalyzing the removal of acetyl and acyl groups from lysine residues. They play pivotal roles in governing cell behaviors and are indispensable in numerous biological processes. HDAC11, the last identified and sole member of class IV HDACs, was reported over a decade ago. However, its physiological function remains poorly understood. Here, we report that HDAC11 knockout mice are resistant to high-fat diet-induced obesity and metabolic syndrome, suggesting that HDAC11 functions as a crucial metabolic regulator. Depletion of HDAC11 significantly enhanced insulin sensitivity and glucose tolerance, attenuated hypercholesterolemia, and decreased hepatosteatosis and liver damage. Mechanistically, HDAC11 deficiency boosts energy expenditure through promoting thermogenic capacity, which attributes to the elevation of uncoupling protein 1 (UCP1) expression and activity in brown adipose tissue. Moreover, loss of HDAC11 activates the adiponectin-AdipoR-AMPK pathway in the liver, which may contribute to a reversal in hepatosteatosis. Overall, our findings distinguish HDAC11 as a novel regulator of obesity, with potentially important implications for obesity-related disease treatment. Keywords: HDAC11, Obesity, Metabolic syndrome, Hepatic steatosis, UCP1, CPT1, Adiponectin |
| first_indexed | 2024-12-13T03:04:40Z |
| format | Article |
| id | doaj.art-bc7cf07b8bf941a3a6bb0f842ecdd4a0 |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-12-13T03:04:40Z |
| publishDate | 2018-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-bc7cf07b8bf941a3a6bb0f842ecdd4a02022-12-22T00:01:45ZengElsevierEBioMedicine2352-39642018-07-0133157168Programming and Regulation of Metabolic Homeostasis by HDAC11Lei Sun0Caralina Marin de Evsikova1Ka Bian2Alexandra Achille3Elphine Telles4Huadong Pei5Edward Seto6George Washington University Cancer Center, USA; Department of Biochemistry & Molecular Medicine, George Washington University School of Medicine & Health Sciences, Washington, DC 20037, USADepartment of Molecular Medicine, Morsani College of Medicine, USAGeorge Washington University Cancer Center, USA; Department of Biochemistry & Molecular Medicine, George Washington University School of Medicine & Health Sciences, Washington, DC 20037, USAMoffitt Cancer Center, University of South Florida, Tampa, FL 33612, USAGeorge Washington University Cancer Center, USAGeorge Washington University Cancer Center, USA; Department of Biochemistry & Molecular Medicine, George Washington University School of Medicine & Health Sciences, Washington, DC 20037, USAGeorge Washington University Cancer Center, USA; Department of Biochemistry & Molecular Medicine, George Washington University School of Medicine & Health Sciences, Washington, DC 20037, USA; Corresponding author at: George Washington University Cancer Center, USA.Histone deacetylases (HDACs) are enzymes that regulate protein functions by catalyzing the removal of acetyl and acyl groups from lysine residues. They play pivotal roles in governing cell behaviors and are indispensable in numerous biological processes. HDAC11, the last identified and sole member of class IV HDACs, was reported over a decade ago. However, its physiological function remains poorly understood. Here, we report that HDAC11 knockout mice are resistant to high-fat diet-induced obesity and metabolic syndrome, suggesting that HDAC11 functions as a crucial metabolic regulator. Depletion of HDAC11 significantly enhanced insulin sensitivity and glucose tolerance, attenuated hypercholesterolemia, and decreased hepatosteatosis and liver damage. Mechanistically, HDAC11 deficiency boosts energy expenditure through promoting thermogenic capacity, which attributes to the elevation of uncoupling protein 1 (UCP1) expression and activity in brown adipose tissue. Moreover, loss of HDAC11 activates the adiponectin-AdipoR-AMPK pathway in the liver, which may contribute to a reversal in hepatosteatosis. Overall, our findings distinguish HDAC11 as a novel regulator of obesity, with potentially important implications for obesity-related disease treatment. Keywords: HDAC11, Obesity, Metabolic syndrome, Hepatic steatosis, UCP1, CPT1, Adiponectinhttp://www.sciencedirect.com/science/article/pii/S2352396418302317 |
| spellingShingle | Lei Sun Caralina Marin de Evsikova Ka Bian Alexandra Achille Elphine Telles Huadong Pei Edward Seto Programming and Regulation of Metabolic Homeostasis by HDAC11 EBioMedicine |
| title | Programming and Regulation of Metabolic Homeostasis by HDAC11 |
| title_full | Programming and Regulation of Metabolic Homeostasis by HDAC11 |
| title_fullStr | Programming and Regulation of Metabolic Homeostasis by HDAC11 |
| title_full_unstemmed | Programming and Regulation of Metabolic Homeostasis by HDAC11 |
| title_short | Programming and Regulation of Metabolic Homeostasis by HDAC11 |
| title_sort | programming and regulation of metabolic homeostasis by hdac11 |
| url | http://www.sciencedirect.com/science/article/pii/S2352396418302317 |
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