Region-specific transcriptomic responses to obesity and diabetes in macaque hypothalamus

作者：Ying Lei, Liang Xian, Yunong Sun, Ting Yao, Hongyu Gong, Zhenhua Chen, Yuanqing Gao, Hui Wang, Ru Wang, Yunqi Huang, Tao Yang, Miao Yu, Longqi Liu, Chun‐Xia Yi, Qingfeng Wu, Xingxing Kong, Xun Xu, Shiping Liu, Zhi Zhang, Tiemin Liu · 发表于：Cell Metabolism · 年份：2024 · DOI：10.1016/j.cmet.2024.01.003 · 被引用次数：39 · 研究领域：Regulation of Appetite and Obesity、Adipose Tissue and Metabolism、Biochemical Analysis and Sensing Techniques

The hypothalamus plays a crucial role in the progression of obesity and diabetes; however, its structural complexity and cellular heterogeneity impede targeted treatments. Here, we profiled the single-cell and spatial transcriptome of the hypothalamus in obese and sporadic type 2 diabetic macaques, revealing primate-specific distributions of clusters and genes as well as spatial region, cell-type-, and gene-feature-specific changes. The infundibular (INF) and paraventricular nuclei (PVN) are most susceptible to metabolic disruption, with the PVN being more sensitive to diabetes. In the INF, obesity results in reduced synaptic plasticity and energy sensing capability, whereas diabetes involves molecular reprogramming associated with impaired tanycytic barriers, activated microglia, and neuronal inflammatory response. In the PVN, cellular metabolism and neural activity are suppressed in diabetic macaques. Spatial transcriptomic data reveal microglia's preference for the parenchyma over the third ventricle in diabetes. Our findings provide a comprehensive view of molecular changes associated with obesity and diabetes.