暴露于慢性社会心理压力是代谢紊乱的危险因素。由于二肽基肽酶 4 (DPP4) 和半胱氨酰组织蛋白酶 K (CTSK) 在人类病理学中发挥着重要作用，因此我们研究了 DPP4 在应激相关脂肪细胞分化中的作用，重点关注胰高血糖素样肽 1（ GLP-1)/脂联素-CTSK 轴体内和体外。来自非应激野生型 (DPP4 / )、DPP4 敲除 (DPP4-/-) 和 CTSK 敲除 (CTSK-/-) 小鼠以及应激 DPP4 / 、DPP4-/-、CTSK- 的血浆和腹股沟脂肪组织/-和DPP4/小鼠接受应激暴露加GLP-1受体激动剂艾塞那肽负荷2周，然后分析应激相关的生物学和/或形态学改变。在慢性应激下的第14天，应激降低了脂肪组织的重量，并导致血浆中DPP4、GLP-1、CTSK、脂联素和肿瘤坏死因子-α蛋白的水平以及CTSK、前脂肪细胞的脂肪组织水平发生有害变化。因子 1、脂肪酸结合蛋白 4、CCAAT/增强子结合蛋白 α、GLP-1 受体、过氧化物酶体增殖物激活受体 γ、perilipin2、分泌型卷曲相关蛋白 4、Wnt5α、Wnt11 和 β-连环蛋白和/或脂肪组织中的mRNA以及巨噬细胞浸润；这些变化通过 DPP4 删除得到纠正。 GLP-1 受体激活和 CTSK 缺失模拟了 DPP4 缺乏对脂肪的益处。在体外，CTSK 沉默和过表达分别阻止和促进应激血清和氧化应激诱导的脂肪细胞分化，并伴随 3T3-L1 细胞中 pref-1、C/EBP-α 和 PPAR-γ 水平的变化。因此，这些发现表明，增加的 DPP4 在应激相关的脂肪细胞分化中发挥着重要作用，可能是通过慢性应激条件下小鼠 GLP-1/脂联素-CTSK 轴激活的负调节而实现的。© 2024 作者。 FASEB 期刊由 Wiley periodicals LLC 代表美国实验生物学学会联合会出版。

Exposure to chronic psychosocial stress is a risk factor for metabolic disorders. Because dipeptidyl peptidase-4 (DPP4) and cysteinyl cathepsin K (CTSK) play important roles in human pathobiology, we investigated the role(s) of DPP4 in stress-related adipocyte differentiation, with a focus on the glucagon-like peptide-1 (GLP-1)/adiponectin-CTSK axis in vivo and in vitro. Plasma and inguinal adipose tissue from non-stress wild-type (DPP4+/+), DPP4-knockout (DPP4-/-) and CTSK-knockout (CTSK-/-) mice, and stressed DPP4+/+, DPP4-/-, CTSK-/-, and DPP4+/+ mice underwent stress exposure plus GLP-1 receptor agonist exenatide loading for 2 weeks and then were analyzed for stress-related biological and/or morphological alterations. On day 14 under chronic stress, stress decreased the weights of adipose tissue and resulted in harmful changes in the plasma levels of DPP4, GLP-1, CTSK, adiponectin, and tumor necrosis factor-α proteins and the adipose tissue levels of CTSK, preadipocyte factor-1, fatty acid binding protein-4, CCAAT/enhancer binding protein-α, GLP-1 receptor, peroxisome proliferator-activated receptor-γ, perilipin2, secreted frizzled-related protein-4, Wnt5α, Wnt11 and β-catenin proteins and/or mRNAs as well as macrophage infiltration in adipose tissue; these changes were rectified by DPP4 deletion. GLP-1 receptor activation and CTSK deletion mimic the adipose benefits of DPP4 deficiency. In vitro, CTSK silencing and overexpression respectively prevented and facilitated stress serum and oxidative stress-induced adipocyte differentiation accompanied with changes in the levels of pref-1, C/EBP-α, and PPAR-γ in 3T3-L1 cells. Thus, these findings indicated that increased DPP4 plays an essential role in stress-related adipocyte differentiation, possibly through a negative regulation of GLP-1/adiponectin-CTSK axis activation in mice under chronic stress conditions.© 2024 The Author(s). The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.