The fat cell senescence hypothesis: a mechanism responsible for abrogating the resolution of inflammation in chronic disease
Purpose of review: Obesity is a chronic inflammatory disease in which the physiological resolution of inflammation is attenuated, leading to low-grade inflammation throughout the body. However, the heat shock response, which is a key component of the physiological response to resolve inflammation, i...
| Main Authors: | , |
|---|---|
| Format: | Journal Article |
| Published: |
Lippincott Williams & Wilkins
2014
|
| Online Access: | http://hdl.handle.net/20.500.11937/12645 |
| _version_ | 1848748133698240512 |
|---|---|
| author | Newsholme, Philip de Bittencourt, P. |
| author_facet | Newsholme, Philip de Bittencourt, P. |
| author_sort | Newsholme, Philip |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | Purpose of review: Obesity is a chronic inflammatory disease in which the physiological resolution of inflammation is attenuated, leading to low-grade inflammation throughout the body. However, the heat shock response, which is a key component of the physiological response to resolve inflammation, is seriously hampered in adipose tissue and other metabolic organs (e.g. skeletal muscle, liver, pancreatic β-cells) in metabolic diseases. In this review, we hypothesize that adipocyte metabolic stress triggers the onset of fat cell senescence, and companion senescence-associated secretory phenotype (SASP), and that such a scenario is responsible for attenuating the resolution of inflammation. Recent findings: We shall discuss the role of the heat shock response in the context of the resolution of inflammation and the relevance of heat shock response blockade in chronic inflammatory diseases. Sirtuin-1 is responsible for the induction of heat shock transcription factor-1 mRNA expression and for the stabilization of heat shock transcription factor-1 in a high-profile activity state. However, adipose tissue-emanated SASP depress sirtuin-1 expression, leading adipocytes to a perpetual state of unresolved inflammation, due to a dampening of the heat shock response. Summary: The advance of inflammasome-mediated SASP from adipose to other tissues promotes cellular senescence in many other cells of the organism, aggravating obesity-dependent chronic inflammation. Inducers of heat shock response (e.g. heat shock itself, physical exercise and calorie restriction) may efficiently interrupt this vicious cycle and are envisaged as the best and also the most economical treatment for obesity-related chronic diseases. |
| first_indexed | 2025-11-14T07:00:12Z |
| format | Journal Article |
| id | curtin-20.500.11937-12645 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T07:00:12Z |
| publishDate | 2014 |
| publisher | Lippincott Williams & Wilkins |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-126452017-09-13T14:59:52Z The fat cell senescence hypothesis: a mechanism responsible for abrogating the resolution of inflammation in chronic disease Newsholme, Philip de Bittencourt, P. Purpose of review: Obesity is a chronic inflammatory disease in which the physiological resolution of inflammation is attenuated, leading to low-grade inflammation throughout the body. However, the heat shock response, which is a key component of the physiological response to resolve inflammation, is seriously hampered in adipose tissue and other metabolic organs (e.g. skeletal muscle, liver, pancreatic β-cells) in metabolic diseases. In this review, we hypothesize that adipocyte metabolic stress triggers the onset of fat cell senescence, and companion senescence-associated secretory phenotype (SASP), and that such a scenario is responsible for attenuating the resolution of inflammation. Recent findings: We shall discuss the role of the heat shock response in the context of the resolution of inflammation and the relevance of heat shock response blockade in chronic inflammatory diseases. Sirtuin-1 is responsible for the induction of heat shock transcription factor-1 mRNA expression and for the stabilization of heat shock transcription factor-1 in a high-profile activity state. However, adipose tissue-emanated SASP depress sirtuin-1 expression, leading adipocytes to a perpetual state of unresolved inflammation, due to a dampening of the heat shock response. Summary: The advance of inflammasome-mediated SASP from adipose to other tissues promotes cellular senescence in many other cells of the organism, aggravating obesity-dependent chronic inflammation. Inducers of heat shock response (e.g. heat shock itself, physical exercise and calorie restriction) may efficiently interrupt this vicious cycle and are envisaged as the best and also the most economical treatment for obesity-related chronic diseases. 2014 Journal Article http://hdl.handle.net/20.500.11937/12645 10.1097/MCO.0000000000000077 Lippincott Williams & Wilkins restricted |
| spellingShingle | Newsholme, Philip de Bittencourt, P. The fat cell senescence hypothesis: a mechanism responsible for abrogating the resolution of inflammation in chronic disease |
| title | The fat cell senescence hypothesis: a mechanism responsible for abrogating the resolution of inflammation in chronic disease |
| title_full | The fat cell senescence hypothesis: a mechanism responsible for abrogating the resolution of inflammation in chronic disease |
| title_fullStr | The fat cell senescence hypothesis: a mechanism responsible for abrogating the resolution of inflammation in chronic disease |
| title_full_unstemmed | The fat cell senescence hypothesis: a mechanism responsible for abrogating the resolution of inflammation in chronic disease |
| title_short | The fat cell senescence hypothesis: a mechanism responsible for abrogating the resolution of inflammation in chronic disease |
| title_sort | fat cell senescence hypothesis: a mechanism responsible for abrogating the resolution of inflammation in chronic disease |
| url | http://hdl.handle.net/20.500.11937/12645 |