The increase in obesity worldwide underlines the need for research concerning its metabolic and genetic determinants. One of the most intriguing mechanisms regarding obesity involves leptin and its signaling cascade. Leptin is a key regulator contributing to the fine‐tuned crosstalk between nutrient availability and appetite signaling in the central nervous system. Owing to ethical concerns, many human tissues are not readily available and pigs can serve as a good animal model owing to their comparable anatomy, metabolism and genetics. In the present study, we utilized the pig to investigate the possible impact of increased adiposity on the development of alterations within the leptin signaling pathway. Two divergent groups of pigs (High and Low) were defined based on a high and low amount of mesenteric fat. Cortex, cerebellum, hypothalamus, mesenteric, subcutaneous and retroperitoneal fat tissues were used to study changes in expression levels of 94 mRNA transcripts related to the leptin signaling pathway using the qPCR approach. No significant differences were found at the central nervous system, whereas the expression level of STAT1 was reduced in mesenteric fat and leptin (LEP) and interleukin 6 (IL6) were shown to be consistently increased in all analyzed fat compartments from pigs with a high amount of mesenteric fat. These results could imply the onset of leptin and pro‐inflammatory cytokine overexpression at early stages of obesity in the analyzed pigs without affecting any key components in the central nervous system. Thus, these pigs showing a unique leptin deregulation in adipose tissues could be a useful translational resource for studies of obesity and leptin resistance phenotypes.

中文翻译：

---

以猪为模型，揭示与瘦素抵抗有关的分子机制

全球肥胖症的增加突显了有关其代谢和遗传决定因素的研究需求。关于肥胖的最引人入胜的机制之一涉及瘦素及其信号转导级联。瘦素是导致中枢神经系统中营养物供应和食欲信号之间微调串扰的关键调节剂。由于道德方面的考虑，许多人体组织不易获得，并且由于其可比的解剖结构，新陈代谢和遗传学，猪可以作为良好的动物模型。在本研究中，我们利用猪来研究肥胖增加对瘦素信号传导途径内变化发展的可能影响。根据肠系膜脂肪的高低定义了两组猪（高和低）。皮质，小脑，下丘脑，肠系膜，皮下和腹膜后脂肪组织用于通过qPCR方法研究与瘦素信号通路相关的94个mRNA转录本的表达水平的变化。在中枢神经系统中未发现显着差异，而中枢神经系统的表达水平STAT1的肠系膜脂肪减少，瘦素（LEP）和白细胞介素6（IL6）在所有分析的具有高肠系膜脂肪的猪脂肪舱中均持续增加。这些结果可能暗示在肥胖的早期阶段瘦肉蛋白和促炎性细胞因子的过表达在分析的猪中不影响中枢神经系统的任​​何关键组成部分。因此，这些猪在脂肪组织中显示出独特的瘦素失调状态，可能是研究肥胖和瘦素抵抗性表型的有用翻译资源。