Department of Nutrition, Food Science and Physiology and Center for Nutrition Research, School of Pharmacy and Nutrition, University of Navarra, Irunlarrea 1, 31008 Pamplona, Spain.
Department of Basic Sciences of Health, Area of Biochemistry and Molecular Biology, Universidad Rey Juan Carlos, Alcorcon, 28933 Madrid, Spain.
Int J Mol Sci. 2023 Jan 31;24(3):2664. doi: 10.3390/ijms24032664.
The aim of this work was to investigate the effect of the whole-body deletion of on the activity of brown adipose tissue and the susceptibility to develop obesity and glucose homeostasis disturbances in mice, especially when subjected to a high fat diet. knockout () and wild type (WT) mice were fed a normal chow diet or a high fat diet (HFD) for 10-weeks. Body weight and composition were assessed. Insulin and glucose tolerance tests and indirect calorimetry assays were performed. Histological analysis of interscapular BAT (iBAT) was carried out, and expression of key genes/proteins involved in BAT function were characterized by qPCR and Western blot. iBAT activity was estimated by F-fluorodeoxyglucose (FDG) uptake with microPET. mice were more prone to develop obesity and insulin resistance, exhibiting increased size of all fat depots. mice displayed a higher respiratory exchange ratio. iBAT presented larger adipocytes in HFD mice, accompanied by downregulation of both and uncoupling protein 1 (UCP1) in parallel with defective insulin signalling. Moreover, HFD mice exhibited impaired response to cold exposure, characterized by a reduced iBAT FDG uptake and difficulty to maintain body temperature when exposed to cold compared to WT HFD mice, suggesting reduced thermogenic capacity. These data suggest that could play a role in BAT activation and in the susceptibility to develop obesity and insulin resistance.
这项工作的目的是研究全身性敲除对棕色脂肪组织活性的影响，以及在高脂肪饮食条件下，肥胖和葡萄糖稳态紊乱易感性的影响。敲除（）和野生型（WT）小鼠分别喂食正常饲料或高脂肪饲料（HFD）10 周。评估体重和体成分。进行胰岛素和葡萄糖耐量试验和间接测热法检测。对肩胛间棕色脂肪组织（iBAT）进行组织学分析，并通过 qPCR 和 Western blot 分析 BAT 功能相关的关键基因/蛋白的表达。通过 microPET 评估 F-氟脱氧葡萄糖（FDG）摄取来估计 iBAT 活性。与 WT HFD 小鼠相比，敲除（）的 HFD 小鼠更容易发生肥胖和胰岛素抵抗，表现为所有脂肪组织的体积增大。敲除（）的 HFD 小鼠的呼吸交换率更高。敲除（）的 HFD 小鼠的 iBAT 中脂肪细胞更大，同时下调（）和解偶联蛋白 1（UCP1），并伴随着胰岛素信号受损。此外，敲除（）的 HFD 小鼠在冷暴露时表现出受损的反应，表现为 iBAT FDG 摄取减少，并且与 WT HFD 小鼠相比，在冷暴露时难以维持体温，这表明其产热能力受损。这些数据表明，在激活棕色脂肪组织和易发生肥胖和胰岛素抵抗方面，可能发挥作用。
