Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, United States of America; James A. Haley Veteran's Hospital, United States of America.
Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, United States of America.
Life Sci. 2023 Dec 15;335:122285. doi: 10.1016/j.lfs.2023.122285. Epub 2023 Nov 22.
The goal of this study was to identify mediators in peri-lymphatic adipose tissue (PLAT) that are altered in obese versus lean Zucker rats, with focus on potential sex differences MAIN METHODS: Mesenteric PLAT was analyzed with protein and lncRNA arrays. Additional RT-PCR confirmation was performed with epididymal/ovarian fat.
MCP-1, TCK-1, Galectin-1, Galectin-3, and neuropilin-1 were elevated in PLAT from obese rats of both sexes. However, 11 additional proteins were elevated only in obese males while 24 different proteins were elevated in obese females. Profiling of lncRNAs revealed lean males have elevated levels of NEAT1, MALAT1 and GAS5 compared to lean females. NEAT1, MALAT1, and GAS5 were significantly reduced with obesity in males but not in females. Another lncRNA, HOTAIR, was higher in lean females compared to males, and its levels in females were reduced with obesity. Obese rats of both sexes had similar histologic findings of mesenteric macrophage crown-like structures and hepatocyte fat accumulation.
While obese male and female Zucker rats both have increased inflammation, they have distinct signals. Future studies of the proteome and lncRNA landscape of obese males vs. females in various animal models and in human subjects are warranted to better guide development of therapeutics for obesity-induced inflammation.
本研究旨在鉴定肥胖与 lean Zucker 大鼠peri-lymphatic 脂肪组织（PLAT）中发生改变的介质，重点关注潜在的性别差异。
采用蛋白质和 lncRNA 芯片分析肠系膜 PLAT。采用附睾/卵巢脂肪进行额外的 RT-PCR 确认。
肥胖大鼠的 PLAT 中 MCP-1、TCK-1、Galectin-1、Galectin-3 和 neuropilin-1 升高。然而，另外 11 种蛋白仅在肥胖雄性大鼠中升高，而另外 24 种蛋白仅在肥胖雌性大鼠中升高。lncRNA 分析显示，与 lean 雌性相比，lean 雄性的 NEAT1、MALAT1 和 GAS5 水平升高。NEAT1、MALAT1 和 GAS5 在雄性肥胖时显著降低，但在雌性中没有。另一种 lncRNA HOTAIR 在 lean 雌性中高于 lean 雄性，肥胖时其在雌性中的水平降低。肥胖的雄性和雌性 Zucker 大鼠均具有相似的肠系膜巨噬细胞冠状结构和肝细胞脂肪堆积的组织学发现。
虽然肥胖的雄性和雌性 Zucker 大鼠均有炎症增加，但它们具有不同的信号。在各种动物模型和人类中，肥胖雄性与雌性的蛋白质组和 lncRNA 图谱的进一步研究对于更好地指导肥胖诱导的炎症治疗方法的发展是必要的。
