Department of Internal Medicine I, Center of Brain, Behavior and Metabolism (CBBM), University of Lübeck, Lübeck, Germany.
Center of Brain, Behavior and Metabolism (CBBM), University of Lübeck, Lübeck, Germany.
Horm Metab Res. 2019 Oct;51(10):678-685. doi: 10.1055/a-0985-4272. Epub 2019 Sep 5.
Nesfatin-1 has originally been established as a bioactive peptide interacting with key hypothalamic nuclei and neural circuitries in control of feeding behavior, while its effect on energy expenditure has only recently been investigated. Hence, the aim of this study was to examine whether centrally acting nesfatin-1 can induce β-adrenergic stimulation, which is a prerequisite for the activation of thermogenic genes and heat release from interscapular brown adipose tissue, key physiological features that underlie increased energy expenditure. This question was addressed in non-fasted mice stereotactically cannulated to receive nesfatin-1 intracerebroventricularly together with peripheral injection of the β-adrenoceptor antagonist SR 59230 A, to assess whole-body energy metabolism. Using a minimally invasive thermography technique, we now demonstrate that the thermogenic effect of an anorectic nesfatin-1 dose critically depends on β adrenergic stimulation, as the co-administration with SR 59230 A completely abolished heat production from interscapular brown adipose tissue and rise in ocular surface temperature, thus preventing body weight loss. Moreover, through indirect calorimetry it could be shown that the anorectic concentration of nesfatin-1 augments overall caloric expenditure. Plausibly, central administration of nesfatin-1 also enhanced the expression of DIO2 and CIDEA mRNA in brown adipose tissue critically involved in the regulation of thermogenesis.
Nesfatin-1 最初被确定为一种生物活性肽，与控制进食行为的下丘脑核和神经回路相互作用，而其对能量消耗的影响最近才被研究。因此，本研究的目的是研究中枢作用的 nesfatin-1 是否可以诱导β-肾上腺素能刺激，这是激活生热基因和从肩胛间棕色脂肪组织释放热量的前提，这是增加能量消耗的关键生理特征。这个问题在非禁食小鼠中通过立体定向套管接受 nesfatin-1 脑室内注射和外周注射β-肾上腺素受体拮抗剂 SR 59230A 来解决，以评估全身能量代谢。使用微创热成像技术，我们现在证明，厌食性 nesfatin-1 剂量的生热作用严重依赖于β肾上腺素能刺激，因为与 SR 59230A 共同给药完全消除了肩胛间棕色脂肪组织的产热和眼表面温度的升高，从而防止体重下降。此外，通过间接测热法可以表明，厌食性浓度的 nesfatin-1 增加了总热量消耗。合理的是，中枢给予 nesfatin-1 还可增强棕色脂肪组织中 DIO2 和 CIDEA mRNA 的表达，这对生热的调节至关重要。
