Cell Metabolism
·
2025
·
IF 30.9
Jianghui Chen,Jing Xiang,Meiyu Zhou,Rongfeng Huang,Jianxin Zhang,Yuanting Cui,Xiaoqing Jiang,Yang Li,Runchao Zhou,Haoran Xin,Jie Li,Lihua Li,Sin Man Lam,Jianfang Zhu,Yanxiu Chen,Qingyuan Yang,Zhifu Xie,Guanghou Shui,Fang Deng,Zhihui Zhang,Min-Dian Li
Feeding rhythms regulate exercise performance and muscle energy metabolism. However, the mechanisms regulating adipocyte functions remain unclear. Here, using multi-omics analyses, involving (phospho-)proteomics and lipidomics, we found that day-restricted feeding (DRF) regulates diurnal rhythms of the mitochondrial proteome, neutral lipidome, and nutrient-sensing pathways in mouse gonadal white adipose tissue (GWAT). Adipocyte-specific knockdown of Prkaa2 (the gene encoding AMPKα2) impairs physical endurance. This defect is associated with altered rhythmicity in acyl-coenzyme A (CoA) metabolism-related genes, a loss of rhythmicity in the GWAT lipidome, and circadian remodeling of serum metabolites—in particular, lactate and succinate. We also found that adipocyte Prkaa2 regulates muscle clock genes during DRF. Notably, oral administration of the AMPK activator C29 increases endurance and muscle functions in a time-of-day manner, which requires intact adipocyte AMPKα2 signaling. Collectively, our work defines adipocyte AMPKα2 signaling as a critical regulator of circadian metabolic coordination between fat and muscle, thereby enhancing exercise performance.
研究领域:
生物化学
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代谢组学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2024
·
IF 4.8
Yichen Hu,Jingzhi Yu,Wanxian He,Yang Qiao,Xie Cheng,Huang Huang,Songqing Lai,Dong Yin,Huan He
The clinical use of doxorubicin has been severely limited by doxorubicin-induced cardiotoxicity (DIC). Its mechanism is extremely complex and involves reactive oxygen species overgeneration, DNA damage, and aberrant inflammatory activity, which also involves multi-regulatory cell death mechanisms, including apoptosis, autophagy, and pyroptosis. These mechanisms overlap and crosstalk, resulting in the poor intervention of DIC injury. Astragaloside IV (Ast) has polybioactivity and mitigates DIC damage; however, the underlying mechanisms remain unknown. This study aimed to investigate whether Ast pretreatment (Ast-pre) could protect the myocardium against DIC damage and the underlying mechanisms. In particular, the relationship between Ast-pre, AMPKα2 activity, autophagy, apoptosis, and pyroptosis was explored. Firstly, DIC injury models were established using neonatal rat cardiomyocytes (NRCMs) and mice. And then the effects of adaptive autophagy, anti-pyroptosis and anti-apoptosis of Ast-pre were detected using multi-relevant indexes in NRCMs. Further, how does Ast-pre in AMPKα2 phosphorylation was explored. Finally, these results were validated by DIC injury in mice. Ast-pre, similar to disulfiram (pyroptosis inhibitor), effectively alleviated the inflammatory response, inhibited oxidative and energy stress, prevented mitochondrial dysfunction, and protected the myocardium resisting DIC damage, as demonstrated using multi-indexes. The protection of Ast-pre to DIC damage was almostly canceled by paclitaxel (pyroptosis inducer), 3-methyladenine (autophagy inhibitor), and pAD/AMPKα2-shRNA or compound C (AMPK inhibitor) to varying degrees. In conclusion, Ast-pre could upregulate and activate AMPKα2, enhance adaptive autophagy, and improve energy metabolism and mitochondrial function, thereby alleviate DIC-induced pyroptosis and apoptosis in NRCMs and mice.
研究领域:
药理学
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心脏病学
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细胞生物学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Shaoyang Zhi,Junli Wang,Yiran Wang,Yijie Li,Mengjuan Zhao,Liping Yang,Chaobin Qin,Xiao Yan,Guoxing Nie
AMPKα1 and AMPKα2, key kinases in regulating energy homeostasis, have not been previously cloned or characterized in common carp ( Cyprinus carpio ). This study identified the open reading frame (ORF) sequences of ampkα1 (1722 bp, encoding 573 amino acids) and ampkα2 (1659 bp, encoding 552 amino acids) through homologous cloning. Sequence alignment and phylogenetic analysis showed a high similarity of both genes with fish homologs. Expression analysis revealed that ampkα1 and ampkα2 are widely expressed across tissues in carp, with ampkα1 highly expressed in the gonads and ampkα2 in the heart. Fasting significantly reduced ampkα1 expression in the heart, adipose tissue, and foregut but increased it in the hindgut and white muscle. Similarly, ampkα2 expression decreased in the hypothalamus and muscle during fasting, with an increase in the midgut. Glucose tolerance tests showed dynamic regulation of ampkα1 and ampkα2 , with initial downregulation followed by upregulation in the hepatopancreas, red muscle, and brain. High-glucose and high-fat diets significantly increased ampkα1 and ampkα2 expression in multiple tissues. Insulin and glucagon treatment induced time-dependent changes in both genes in hepatocytes, while Aeromonas hydrophila infection, LPS, and Poly (I:C) stimulation upregulated ampkα1 and ampkα2 in immune-related tissues. Knockdown of ampkα2 , but not ampkα1 , reduced glut1b mRNA levels, while both knockdowns of ampkα1 and ampkα2 promoted the expression of gsk3β , pygm , acc , fas , srebp , cs , and pro-inflammatory cytokines, suggesting their involvement in metabolic and immune regulation in carp.
研究领域:
分子生物学
·
营养学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）