Chen Yen-Wei, Ahn In Sook, Wang Susanna Sue-Ming, Majid Sana, Diamante Graciel, Cely Ingrid, Zhang Guanglin, Cabanayan Angelus, Komzyuk Sergey, Bonnett Jack, Arneson Douglas, Yang Xia
Department of Integrative Biology & Physiology, University of California, Los Angeles, Los Angeles, CA, USA; Interdepartmental Program of Molecular Toxicology, University of California, Los Angeles, Los Angeles, CA, USA.
Department of Integrative Biology & Physiology, University of California, Los Angeles, Los Angeles, CA, USA.
Cell Rep. 2025 May 27;44(5):115690. doi: 10.1016/j.celrep.2025.115690. Epub 2025 May 10.
Metabolic syndrome (MetS), a conglomerate of dysregulated metabolic traits that vary between individuals, is partially driven by modern diets high in fat, sucrose, or fructose and their interactions with host genes in metabolic tissues. To elucidate the roles of individual tissues and cell types in diet-induced MetS, we performed single-cell RNA sequencing on the hypothalamus, liver, adipose tissue, and small intestine of mice fed high-fat high-sucrose (HFHS) or fructose diets. We found that hypothalamic neurons were sensitive to fructose, while adipose progenitor cells and macrophages were responsive to HFHS. Ligand-receptor analysis revealed lipid metabolism and inflammation networks among peripheral tissues driven by HFHS, while both diets stimulated synaptic remodeling within the hypothalamus. mt-Rnr2, a top responder to both diets, mitigated diet-induced MetS by stimulating thermogenesis. Our study demonstrates that HFHS and fructose diets have differential cell type and network targets but also share regulators such as mt-Rnr2 to affect MetS risk.
代谢综合征（MetS）是一种个体间代谢特征失调的集合，部分由高脂肪、蔗糖或果糖的现代饮食及其与代谢组织中宿主基因的相互作用所驱动。为了阐明个体组织和细胞类型在饮食诱导的代谢综合征中的作用，我们对喂食高脂高蔗糖（HFHS）或果糖饮食的小鼠的下丘脑、肝脏、脂肪组织和小肠进行了单细胞RNA测序。我们发现下丘脑神经元对果糖敏感，而脂肪祖细胞和巨噬细胞对HFHS有反应。配体-受体分析揭示了由HFHS驱动的外周组织中的脂质代谢和炎症网络，而两种饮食都刺激了下丘脑内的突触重塑。mt-Rnr2是对两种饮食反应最强的基因，它通过刺激产热来减轻饮食诱导的代谢综合征。我们的研究表明，HFHS和果糖饮食具有不同的细胞类型和网络靶点，但也共享如mt-Rnr2等调节因子来影响代谢综合征风险。
