Increased adipose mass can cause insulin resistance and type 2 diabetes mellitus. This phenomenon is related to adipocyte-secreted signaling molecules that affect glucose balance, such as fatty acids, adiponectin, leptin, interleukin-6, tumor necrosis factor-α, and resistin. Among these hormones, leptin and resistin play important roles in regulating weight and glucose metabolism. Leptin and resistin work in both similar and opposite ways, and they interact with each other. Circulating concentrations of leptin and resistin are elevated in models of obesity and rodents fed a high-fat diet. In addition, leptin and resistin are similarly regulated by nutritional status: they are reduced by fasting and increased by feeding. This effect is mediated partially through insulin receptors and glucose transporters. Our latest data provided the first indication that in sheep, intravenous infusion of resistin increases the mean circulating concentrations of leptin and decreases luteinizing hormone in a dose-dependent manner during both the long-day (LD) and short-day seasons. Furthermore, exogenous resistin increased suppressor of cytokine signaling (SOCS)-3 mRNA expression only during the LD season, when the leptin resistance/insensitivity phenomenon was observed in the arcuate nucleus, preoptic area, and anterior pituitary. We concluded that one factor contributing to central leptin resistance is autosuppression, via which leptin and resistin stimulate the expression of SOCS-3, which inhibits leptin signaling. The increased expression of SOCS-3 in response to leptin and resistin may be a pivotal cause of leptin resistance/insensitivity, a pathological situation in obese individuals and a physiological occurrence in sheep during the LD season.

增加的脂肪量会导致胰岛素抵抗和 2 型糖尿病。这种现象与影响葡萄糖平衡的脂肪细胞分泌的信号分子有关，如脂肪酸、脂联素、瘦素、白细胞介素-6、肿瘤坏死因子-α和抵抗素。在这些激素中，瘦素和抵抗素在调节体重和葡萄糖代谢方面起着重要作用。瘦素和抵抗素以相似和相反的方式起作用，并且它们相互作用。在肥胖模型和喂食高脂肪饮食的啮齿动物模型中，瘦素和抵抗素的循环浓度升高。此外，瘦素和抵抗素同样受营养状况的调节：禁食时减少，进食时增加。这种作用部分是通过胰岛素受体和葡萄糖转运蛋白介导的。我们的最新数据首次表明，在绵羊中，静脉输注抵抗素会增加瘦素的平均循环浓度，并在长日照 (LD) 和短日照季节期间以剂量依赖性方式降低促黄体生成素。此外，外源性抵抗素仅在 LD 季节增加细胞因子信号 (SOCS)-3 mRNA 表达的抑制因子，此时在弓状核、视前区和垂体前叶中观察到瘦素抵抗/不敏感现象。我们得出结论，导致中枢瘦素抵抗的一个因素是自身抑制，通过这种抑制，瘦素和抵抗素刺激了 在长日照 (LD) 和短日照季节，静脉输注抵抗素以剂量依赖性方式增加瘦素的平均循环浓度并降低促黄体生成素。此外，外源性抵抗素仅在 LD 季节增加细胞因子信号 (SOCS)-3 mRNA 表达的抑制因子，此时在弓状核、视前区和垂体前叶中观察到瘦素抵抗/不敏感现象。我们得出结论，导致中枢瘦素抵抗的一个因素是自身抑制，通过这种抑制，瘦素和抵抗素刺激了 在长日照 (LD) 和短日照季节，静脉输注抵抗素以剂量依赖性方式增加瘦素的平均循环浓度并降低促黄体生成素。此外，外源性抵抗素仅在 LD 季节增加细胞因子信号 (SOCS)-3 mRNA 表达的抑制因子，此时在弓状核、视前区和垂体前叶中观察到瘦素抵抗/不敏感现象。我们得出结论，导致中枢瘦素抵抗的一个因素是自身抑制，通过这种抑制，瘦素和抵抗素刺激了 视前区和垂体前叶。我们得出结论，导致中枢瘦素抵抗的一个因素是自身抑制，通过这种抑制，瘦素和抵抗素刺激了 视前区和垂体前叶。我们得出结论，导致中枢瘦素抵抗的一个因素是自身抑制，通过这种抑制，瘦素和抵抗素刺激了SOCS-3，抑制瘦素信号。SOCS-3响应瘦素和抵抗素的表达增加可能是瘦素抵抗/不敏感、肥胖个体的病理状况和 LD 季节绵羊的生理发生的关键原因。