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Nobiletin Protects Against Alcoholic Liver Disease in Mice via the BMAL1-AKT-Lipogenesis Pathway.
Li, Xudong; Zhuang, Runxuan; Zhang, Ke; Zhang, Yuchun; Lu, Zhitian; Wu, Fan; Wu, Xiaoli; Li, Wenxue; Zhang, Zheqing; Zhang, Huijie; Zhu, Wei; Zhang, Bo.
Afiliación
  • Li X; Food Safety and Health Research Center, School of Public Health, Southern Medical University, Guangzhou, Guangdong, 510515, China.
  • Zhuang R; Department of Toxicological and Biochemical Test, Guangzhou Center for Disease Control and Prevention, Guangzhou, Guangdong, 510440, China.
  • Zhang K; Food Safety and Health Research Center, School of Public Health, Southern Medical University, Guangzhou, Guangdong, 510515, China.
  • Zhang Y; Food Safety and Health Research Center, School of Public Health, Southern Medical University, Guangzhou, Guangdong, 510515, China.
  • Lu Z; Food Safety and Health Research Center, School of Public Health, Southern Medical University, Guangzhou, Guangdong, 510515, China.
  • Wu F; Food Safety and Health Research Center, School of Public Health, Southern Medical University, Guangzhou, Guangdong, 510515, China.
  • Wu X; Food Safety and Health Research Center, School of Public Health, Southern Medical University, Guangzhou, Guangdong, 510515, China.
  • Li W; Food Safety and Health Research Center, School of Public Health, Southern Medical University, Guangzhou, Guangdong, 510515, China.
  • Zhang Z; Department of Toxicological and Biochemical Test, Guangzhou Center for Disease Control and Prevention, Guangzhou, Guangdong, 510440, China.
  • Zhang H; Department of Nutrition and Food Hygiene, School of Public Health, Southern Medical University, Guangzhou, Guangdong, 510515, China.
  • Zhu W; Department of Endocrinology and Metabolism, Guangdong Provincial Key Laboratory of Shock and Microcirculation, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, China.
  • Zhang B; Department of Toxicological and Biochemical Test, Guangzhou Center for Disease Control and Prevention, Guangzhou, Guangdong, 510440, China.
Mol Nutr Food Res ; 68(12): e2300833, 2024 Jun.
Article en En | MEDLINE | ID: mdl-38850176
ABSTRACT
SCOPE Alcoholic liver disease (ALD) is a global public health concern. Nobiletin, a polymethoxyflavone abundant in citrus fruits, enhances circadian rhythms and ameliorates diet-induced hepatic steatosis, but its influences on ALD are unknown. This study investigates the role of brain and muscle Arnt-like protein-1 (Bmal1), a key regulator of the circadian clock, in nobiletin-alleviated ALD. METHODS AND

RESULTS:

This study uses chronic ethanol feeding plus an ethanol binge to establish ALD models in Bmal1flox/flox and Bmal1 liver-specific knockout (Bmal1LKO) mice. Nobiletin mitigates ethanol-induced liver injury (alanine aminotransferase [ALT]), glucose intolerance, hepatic apoptosis, and lipid deposition (triglyceride [TG], total cholesterol [TC]) in Bmal1flox/flox mice. Nobiletin fails to modulated liver injury (ALT, aspartate aminotransferase [AST]), apoptosis, and TG accumulation in Bmal1LKO mice. The expression of lipogenic genes (acetyl-CoA carboxylase alpha [Acaca], fatty acid synthase [Fasn]) and fatty acid oxidative genes (carnitine pamitoyltransferase [Cpt1a], cytochrome P450, family 4, subfamily a, polypeptide 10 [Cyp4a10], and cytochrome P450, family4, subfamily a, polypeptide 14 [Cyp4a14]) is inhibited, and the expression of proapoptotic genes (Bcl2 inteacting mediator of cell death [Bim]) is enhanced by ethanol in Bmal1flox/flox mice. Nobiletin antagonizes the expression of these genes in Bmal1flox/flox mice and not in Bmal1LKO mice. Nobiletin activates protein kinase B (PKB, also known as AKT) phosphorylation, increases the levels of the carbohydrate response element binding protein (ChREBP), ACC1, and FASN, and reduces the level of sterol-regulatory element binding protein 1 (SREBP1) and phosphorylation of ACC1 in a Bmal1-dependent manner.

CONCLUSION:

Nobiletin alleviates ALD by increasing the expression of genes involved in fatty acid oxidation by increasing AKT phosphorylation and lipogenesis in a Bmal1-dependent manner.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ratones Noqueados / Flavonas / Proteínas Proto-Oncogénicas c-akt / Lipogénesis / Factores de Transcripción ARNTL / Hepatopatías Alcohólicas Límite: Animals Idioma: En Revista: Mol Nutr Food Res Asunto de la revista: CIENCIAS DA NUTRICAO Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Alemania
Texto completo
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Imprimir
XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ratones Noqueados / Flavonas / Proteínas Proto-Oncogénicas c-akt / Lipogénesis / Factores de Transcripción ARNTL / Hepatopatías Alcohólicas Límite: Animals Idioma: En Revista: Mol Nutr Food Res Asunto de la revista: CIENCIAS DA NUTRICAO Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Alemania