High-Fat Diet Triggers Inflammation-Induced Cleavage of SIRT1 in Adipose Tissue To Promote Metabolic Dysfunction
Adipose tissue plays an important role in storing excess nutrients and preventing ectopic lipid accumulation in other organs. Obesity leads to excess lipid storage in adipocytes, resulting in the generation of stress signals and the derangement of metabolic functions. SIRT1 is an important regulator...
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| Format: | Article |
| Language: | en_US |
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Elsevier
2014
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| Online Access: | http://hdl.handle.net/1721.1/91624 https://orcid.org/0000-0003-4064-2510 |
| _version_ | 1826202903583391744 |
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| author | Chalkiadaki, Angeliki Guarente, Leonard Pershing |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Chalkiadaki, Angeliki Guarente, Leonard Pershing |
| author_sort | Chalkiadaki, Angeliki |
| collection | MIT |
| description | Adipose tissue plays an important role in storing excess nutrients and preventing ectopic lipid accumulation in other organs. Obesity leads to excess lipid storage in adipocytes, resulting in the generation of stress signals and the derangement of metabolic functions. SIRT1 is an important regulatory sensor of nutrient availability in many metabolic tissues. Here we report that SIRT1 functions in adipose tissue to protect from inflammation and obesity under normal feeding conditions, and to forestall the progression to metabolic dysfunction under dietary stress and aging. Genetic ablation of SIRT1 in adipose tissue leads to gene expression changes that highly overlap with changes induced by high-fat diet in wild-type mice, suggesting that dietary stress signals inhibit the activity of SIRT1. Indeed, we show that high-fat diet induces the cleavage of SIRT1 protein in adipose tissue by the inflammation-activated caspase-1, providing a link between dietary stress and predisposition to metabolic dysfunction. |
| first_indexed | 2024-09-23T12:24:14Z |
| format | Article |
| id | mit-1721.1/91624 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T12:24:14Z |
| publishDate | 2014 |
| publisher | Elsevier |
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| spelling | mit-1721.1/916242022-10-01T09:06:39Z High-Fat Diet Triggers Inflammation-Induced Cleavage of SIRT1 in Adipose Tissue To Promote Metabolic Dysfunction Chalkiadaki, Angeliki Guarente, Leonard Pershing Massachusetts Institute of Technology. Department of Biology Paul F. Glenn Center for Biology of Aging Research (Massachusetts Institute of Technology) Chalkiadaki, Angeliki Guarente, Leonard Pershing Adipose tissue plays an important role in storing excess nutrients and preventing ectopic lipid accumulation in other organs. Obesity leads to excess lipid storage in adipocytes, resulting in the generation of stress signals and the derangement of metabolic functions. SIRT1 is an important regulatory sensor of nutrient availability in many metabolic tissues. Here we report that SIRT1 functions in adipose tissue to protect from inflammation and obesity under normal feeding conditions, and to forestall the progression to metabolic dysfunction under dietary stress and aging. Genetic ablation of SIRT1 in adipose tissue leads to gene expression changes that highly overlap with changes induced by high-fat diet in wild-type mice, suggesting that dietary stress signals inhibit the activity of SIRT1. Indeed, we show that high-fat diet induces the cleavage of SIRT1 protein in adipose tissue by the inflammation-activated caspase-1, providing a link between dietary stress and predisposition to metabolic dysfunction. National Institutes of Health (U.S.) Glenn Foundation for Medical Research American Heart Association (Postdoctoral Fellowship) 2014-11-20T13:16:34Z 2014-11-20T13:16:34Z 2012-08 2012-03 Article http://purl.org/eprint/type/JournalArticle 15504131 http://hdl.handle.net/1721.1/91624 Chalkiadaki, Angeliki, and Leonard Guarente. “High-Fat Diet Triggers Inflammation-Induced Cleavage of SIRT1 in Adipose Tissue To Promote Metabolic Dysfunction.” Cell Metabolism 16, no. 2 (August 2012): 180–188. © 2012 Elsevier Inc. https://orcid.org/0000-0003-4064-2510 en_US http://dx.doi.org/10.1016/j.cmet.2012.07.003 Cell Metabolism Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Elsevier Elsevier |
| spellingShingle | Chalkiadaki, Angeliki Guarente, Leonard Pershing High-Fat Diet Triggers Inflammation-Induced Cleavage of SIRT1 in Adipose Tissue To Promote Metabolic Dysfunction |
| title | High-Fat Diet Triggers Inflammation-Induced Cleavage of SIRT1 in Adipose Tissue To Promote Metabolic Dysfunction |
| title_full | High-Fat Diet Triggers Inflammation-Induced Cleavage of SIRT1 in Adipose Tissue To Promote Metabolic Dysfunction |
| title_fullStr | High-Fat Diet Triggers Inflammation-Induced Cleavage of SIRT1 in Adipose Tissue To Promote Metabolic Dysfunction |
| title_full_unstemmed | High-Fat Diet Triggers Inflammation-Induced Cleavage of SIRT1 in Adipose Tissue To Promote Metabolic Dysfunction |
| title_short | High-Fat Diet Triggers Inflammation-Induced Cleavage of SIRT1 in Adipose Tissue To Promote Metabolic Dysfunction |
| title_sort | high fat diet triggers inflammation induced cleavage of sirt1 in adipose tissue to promote metabolic dysfunction |
| url | http://hdl.handle.net/1721.1/91624 https://orcid.org/0000-0003-4064-2510 |
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