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Dietary long-chain fatty acids promote colitis by regulating palmitoylation of STAT3 through CD36-mediated endocytosis.
Wei, Yuping; Li, Jinting; Li, Jiao; Liu, Chuan; Guo, Xingzhou; Liu, Zhengru; Zhang, Luyun; Bao, Shenglan; Wu, Xiaohan; Su, Wenhao; Wang, Xiaoli; Zhang, Jixiang; Dong, Weiguo.
Afiliación
  • Wei Y; Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China.
  • Li J; Key Laboratory of Hubei Province for Digestive System Disease, Wuhan, Hubei Province, China.
  • Li J; Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China.
  • Liu C; Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China.
  • Guo X; Key Laboratory of Hubei Province for Digestive System Disease, Wuhan, Hubei Province, China.
  • Liu Z; Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China.
  • Zhang L; Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China.
  • Bao S; Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China.
  • Wu X; Key Laboratory of Hubei Province for Digestive System Disease, Wuhan, Hubei Province, China.
  • Su W; Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China.
  • Wang X; Key Laboratory of Hubei Province for Digestive System Disease, Wuhan, Hubei Province, China.
  • Zhang J; Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China.
  • Dong W; Key Laboratory of Hubei Province for Digestive System Disease, Wuhan, Hubei Province, China.
Cell Death Dis ; 15(1): 60, 2024 01 17.
Article en En | MEDLINE | ID: mdl-38233383
ABSTRACT
The Western diet, characterized by its high content of long-chain fatty acids (LCFAs), is widely recognized as a significant triggering factor for inflammatory bowel disease (IBD). While the link between a high-fat diet and colitis has been observed, the specific effects and mechanisms remain incompletely understood. Our study provides evidence that the diet rich in LCFAs can disrupt the integrity of the intestinal barrier and exacerbate experimental colitis in mice. Mechanistically, LCFAs upregulate the signal transducer and activator of transcription-3 (STAT3) pathway in the inflammatory model, and STAT3 knockout effectively counters the pro-inflammatory effects of LCFAs on colitis. Specifically, palmitic acid (PA), a representative LCFA, enters intestinal epithelial cells via the cluster of differentiation 36 (CD36) pathway and participates in the palmitoylation cycle of STAT3. Inhibiting this cycle using pharmacological inhibitors like 2-Bromopalmitate (2-BP) and ML349, as well as DHHC7 knockdown, has the ability to alleviate inflammation induced by PA. These findings highlight the significant role of dietary LCFAs, especially PA, in the development and progression of IBD. Diet adjustments and targeted modulation offer potential therapeutic strategies for managing this condition. Model of LCFAs involvement in the palmitoylation cycle of STAT3 upon internalization into cells. Following cellular uptake through CD36, LCFAs are converted to palmitoyl-CoA. In the presence of DHHC7, palmitoyl-CoA binds to STAT3 at the C108 site, forming palmitoylated STAT3. Palmitoylation further promotes phosphorylation at the Y705 site of STAT3. Subsequently, palmitoylated STAT3 undergoes depalmitoylation by APT2 and translocates to the nucleus to exert its biological functions.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedades Inflamatorias del Intestino / Colitis Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Cell Death Dis Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedades Inflamatorias del Intestino / Colitis Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Cell Death Dis Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido