Division of Endocrinology and Metabolism, Department of Homeostatic Regulation, National Institute for Physiological Sciences, National Institutes of Natural Sciences, Okazaki, Aichi 444-8585, Japan; Graduate Institute for Advanced Studies, SOKENDAI, Okazaki, Aichi 444-8585, Japan.
Division of Endocrinology and Metabolism, Department of Homeostatic Regulation, National Institute for Physiological Sciences, National Institutes of Natural Sciences, Okazaki, Aichi 444-8585, Japan; Graduate Institute for Advanced Studies, SOKENDAI, Okazaki, Aichi 444-8585, Japan.
Cell Rep. 2023 Jun 27;42(6):112627. doi: 10.1016/j.celrep.2023.112627. Epub 2023 Jun 19.
Inflammation and thermogenesis in white adipose tissue (WAT) at different sites influence the overall effects of obesity on metabolic health. In mice fed a high-fat diet (HFD), inflammatory responses are less pronounced in inguinal WAT (ingWAT) than in epididymal WAT (epiWAT). Here we show that ablation and activation of steroidogenic factor 1 (SF1)-expressing neurons in the ventromedial hypothalamus (VMH) oppositely affect the expression of inflammation-related genes and the formation of crown-like structures by infiltrating macrophages in ingWAT, but not in epiWAT, of HFD-fed mice, with these effects being mediated by sympathetic nerves innervating ingWAT. In contrast, SF1 neurons of the VMH preferentially regulated the expression of thermogenesis-related genes in interscapular brown adipose tissue (BAT) of HFD-fed mice. These results suggest that SF1 neurons of the VMH differentially regulate inflammatory responses and thermogenesis among various adipose tissue depots and restrain inflammation associated with diet-induced obesity specifically in ingWAT.
在不同部位的白色脂肪组织（WAT）中，炎症和产热会影响肥胖对代谢健康的整体影响。在高脂饮食（HFD）喂养的小鼠中，腹股沟 WAT（ingWAT）的炎症反应比附睾 WAT（epiWAT）不那么明显。在这里，我们表明，在下丘脑腹内侧核（VMH）中表达甾体生成因子 1（SF1）的神经元的消融和激活，会对 HFD 喂养小鼠的 ingWAT 中浸润巨噬细胞形成的与炎症相关基因的表达和冠状结构的形成产生相反的影响，但不会对 epiWAT 产生影响，这些影响是由支配 ingWAT 的交感神经介导的。相比之下，VMH 的 SF1 神经元优先调节 HFD 喂养小鼠肩胛间棕色脂肪组织（BAT）中与产热相关的基因表达。这些结果表明，VMH 的 SF1 神经元在不同的脂肪组织库中差异调节炎症反应和产热，并特异性地抑制 ingWAT 中与饮食诱导肥胖相关的炎症。
