Yingxi Xu, Chen Wang, Ping-Chih Ho·29 May 2025
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Circadian rhythms are fundamental regulators of physiological processes, including immune function. Recent insights uncover that not only lymphocytes but also myeloid cells possess intrinsic circadian clocks that govern their behavior and function. Emerging evidence highlights how circadian regulation of metabolism critically shapes the inflammatory and tissue-repair functions of myeloid subsets. Furthermore, mitochondrial dynamics, a key metabolic feature, are under circadian control and influence antigen presentation and effector functions. Here, we review the interplay between circadian clocks, metabolism, and myeloid immunity, discussing their therapeutic opportunities for optimizing vaccination, infection management, and immunotherapy.
Shuang Han, Lu Jin, Wei Peng, Xue Lv, Ziyin Zhang, Tongyu Liu, Lin Mi, Yue Gao, Jun-fen Fu, Zhuo-Xian Meng·04 May 2025
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Skeletal muscle plays a key role in metabolic homeostasis. Brg1/Brm-associated factor (Baf) 60c, a subunit of the mating type switching/sucrose non-fermenting (SWI/SNF) chromatin remodeling complexes, was previously identified to be robustly involved in glycolytic muscle function and systemic metabolic balance. However, whether Baf60c regulates the secreted factors and couples the skeletal muscle function to systemic metabolism remains unclear. Here, we uncover that Baf60c regulates the expression of a series of secreted factors, among which Musclin, a recently identified negative regulator of beige adipocyte thermogenesis, was top-ranked in the upregulated factors in Baf60c-deficient muscle. Mechanistically, Baf60c physically interacts with the transcription factor myocyte enhancer factor 2c (Mef2c) and modulates the chromatin accessibility at the proximal promoter regions upstream of the Musclin gene transcription start site (TSS), therefore negatively regulating Musclin gene expression in the skeletal muscle. Further in vivo metabolic assays demonstrate that muscle-specific Baf60c ablation inhibits thermogenesis and elevates blood glucose. Conversely, muscle-specific overexpression of Baf60c increases thermogenesis and energy expenditure and improves systemic glucose metabolism. Together, this work uncovers Baf60c/Mef2c-mediated chromatin remodeling signaling in myocytes that control adipose tissue thermogenesis and systemic metabolism through Musclin-mediated muscle-fat crosstalk.
Yin-Yue Zhao, Yi-Fan Li, Jian-Wei Hao, Ning Zhao, Xiao-Ting Men, Xiao-Yu Bai, Rui Tai, Hao-Bin Ye, Xing-Rong Du, Hui-Ling Guo, Juan Wang, Hong-Jie Qian, Tong-Jin Zhao·10 Apr 2025
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The intestinal lymphatic system is essential for lipid absorption, yet its regulatory mechanisms remain poorly understood. Here, we identify DHHC5, an Asp-His-His-Cys (DHHC) motif-containing palmitoyl acyltransferase, as a critical regulator of intestinal lymphatic integrity and lipid uptake. Whole-body inducible Dhhc5 knockout (Dhhc5-IKO) mice were resistant to diet-induced obesity and exhibited impaired intestinal lipid absorption due to lymphatic dysfunction. Similar defects were observed upon specific knockout of DHHC5 in lymphatic endothelial cells (LECs), underscoring its cell-autonomous role. Mechanistically, DHHC5 facilitates vascular endothelial growth factor receptor 2 (VEGFR2) signaling by promoting its lipid raft localization in LECs. We further identified CRYBG1, an actin-binding protein, as the substrate of DHHC5. CRYBG1 interacts with VEGFR2, and its palmitoylation is required for the lipid raft localization of VEGFR2. These findings reveal a DHHC5-CRYBG1-VEGFR2 axis that governs intestinal lymphatic function and lipid absorption, providing new insights into the regulation of dietary lipid metabolism.
Haoqi Zhang, Tengteng Huang, Xianyang Jin, Siyuan Liu, Yi Yang, Luting Liu, Xuemei Jiang, Ruinan Zhang, Hui Ye, Xinyue Qi, Tongxing Song, Chao Jin, Bin Feng, Lianqiang Che, Shengyu Xu, Yan Lin, Zhengfeng Fang, Ting Luo, Yong Zhuo, De Wu, Lun Hua·25 Mar 2025
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Time-restricted feeding (TRF) is a dietary strategy used to prevent and treat obesity in both sexes. However, TRF affects liver metabolism differently in males and females, and the mechanisms behind these differences remain unclear. Our study reveals that during TRF, female livers are more likely to break down amino acids (AAs) to synthesize fats, while male livers significantly reduce fatty acid synthesis. The changes in the liver’s AA metabolic profile after gonadectomy suggest that estrogen signaling is crucial for regulating AA metabolism in females during TRF. Additionally, we demonstrate that hepatic estrogen receptor α (ERα)-mediated AA metabolism contributes to the sex-specific effects of TRF on liver metabolism. These findings offer new insights into the molecular mechanisms of TRF and its potential clinical application for treating fatty liver and other metabolic disorders. They also emphasize the need to consider sex differences when developing nutritional and pharmacological treatments for metabolic diseases in females.
