Bruun Jens M, Pedersen Steen B, Kristensen Kurt, Richelsen Bjørn
Department of Endocrinology and Metabolism C, Aarhus Amtssygehus, Aarhus University Hospital and Faculty of Health Sciences, Aarhus University, Tage Hansensgade 2, Denmark.
Mol Cell Endocrinol. 2002 Apr 25;190(1-2):91-9. doi: 10.1016/s0303-7207(02)00007-2.
Leptin is synthesized in adipocytes and acts primarily through central pathways suppressing appetite and increasing the metabolic rate in rodents as well as in humans. Recently leptin has also been suggested to have peripheral effects and be involved in insulin action. Since cytokines and chemokines may have effects on appetite regulation as well as on some of the obesity-related complications e.g. insulin resistance and cardiovascular disease, we investigated the effects of various cytokines and chemokines on leptin production in human adipose tissue fragments in vitro. Abdominal subcutaneous adipose tissue from healthy normal to overweight females was incubated for up to 48 h with the cytokines: tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and interleukin-1beta (IL-1beta) and the chemokine: interleukin-8 (IL-8). IL-1beta (50 ng/ml) and TNF-alpha (10 ng/ml) decreased leptin production by 30-50% (P<0.05) and gene expression by 80-90% (P<0.05). In contrast, IL-6 and IL-8 had no effect on either leptin production or leptin gene expression. Interestingly, IL-1beta elicited a biphasic effect on leptin release with an incremental phase observed within 4 h with no concomitant change in leptin gene expression, followed by a long-lasting inhibition of leptin release and leptin gene expression. This could suggest that IL-1beta through a post-translational pathway induced an acute increase in leptin-secretion, perhaps through the release of leptin from a pre-formed pool within the adipose tissue. The long-term decrease in both leptin secretion and transcription could indicate that pro-inflammatory cytokines such as IL-1beta and TNF-alpha might influence the circulating leptin levels and thereby influence the adipose tissue to brain signalling, which could be of importance in relation to the obesity-associated diseases such as insulin resistance and cardiovascular disease.
瘦素在脂肪细胞中合成，主要通过中枢途径发挥作用，在啮齿动物和人类中抑制食欲并提高代谢率。最近，瘦素也被认为具有外周作用，并参与胰岛素作用。由于细胞因子和趋化因子可能对食欲调节以及一些与肥胖相关的并发症（如胰岛素抵抗和心血管疾病）产生影响，我们在体外研究了各种细胞因子和趋化因子对人脂肪组织片段中瘦素产生的影响。将健康正常至超重女性的腹部皮下脂肪组织与细胞因子肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）和白细胞介素-1β（IL-1β）以及趋化因子白细胞介素-8（IL-8）一起孵育长达48小时。IL-1β（50 ng/ml）和TNF-α（10 ng/ml）使瘦素产生减少30 - 50%（P<0.05），基因表达减少80 - 90%（P<0.05）。相比之下，IL-6和IL-8对瘦素产生或瘦素基因表达均无影响。有趣的是，IL-1β对瘦素释放产生双相作用，在4小时内观察到递增阶段，瘦素基因表达无相应变化，随后是对瘦素释放和瘦素基因表达的长期抑制。这可能表明IL-1β通过翻译后途径诱导瘦素分泌急性增加，可能是通过从脂肪组织中预先形成的池中释放瘦素。瘦素分泌和转录的长期减少可能表明，诸如IL-1β和TNF-α等促炎细胞因子可能影响循环瘦素水平，从而影响脂肪组织向大脑的信号传递，这可能与胰岛素抵抗和心血管疾病等肥胖相关疾病有关。
