EA 3533, Laboratory of Metabolic Adaptations to Exercise in Physiological and Pathological Conditions, Clermont University, Blaise Pascal University, BP 10448, 63000 Clermont-Ferrand, France; Clermont University, Auvergne University, Human Nutrition Unit, BP 10448, 63000 Clermont-Ferrand cedex 1, France.
Zensun Sci and Tech Ltd., Shanghai, China.
Diabetes Metab. 2015 Apr;41(2):168-72. doi: 10.1016/j.diabet.2014.12.002. Epub 2015 Jan 5.
Studies in vitro have highlighted the potential involvement of neuregulin 1 (NRG1) in the regulation of energy metabolism. This effect has also been suggested in vivo, as intracerebroventricular injection of NRG1 reduces food intakes and weight gain in rodents. Thus, it was hypothesised that NRG1 might affect serum leptin levels in mice.
Weight, food intakes, energy expenditure, spontaneous physical activity and serum leptin levels were evaluated in normal-weight C57BL/6JRJ mice following intraperitoneal administration of NRG1 (50 μg/kg, three times/week) or saline for 8 weeks. Based on the results of this first experiment, leptin-resistant obese db/db mice were then given NRG1 for 8 weeks.
Leptin serum concentrations were six times higher in C57BL/6JRJ mice treated with NRG1 than in the animals given saline. NRG1 treatment also reduced weight gain by 10% and food intakes by 15% compared with saline treatment, while energy expenditure remained unchanged. In db/db mice, serum leptin concentrations, weight gain, food intakes, energy expenditure and spontaneous physical activity were not altered by NRG1 treatment.
The decrease in food intakes and weight gain associated with NRG1 treatment in C57BL/6JRJ mice may be partly explained by increased leptin levels, whereas db/db mice were not affected by the treatment, suggesting resistance to NRG1 in this pathological state.
体外研究已经强调了神经调节蛋白 1(NRG1)在调节能量代谢中的潜在作用。这种作用在体内也有提示,因为脑室注射 NRG1 可减少啮齿动物的食物摄入量和体重增加。因此,研究人员假设 NRG1 可能会影响小鼠的血清瘦素水平。
在正常体重的 C57BL/6JRJ 小鼠中,通过腹腔内给予 NRG1(50μg/kg,每周 3 次)或生理盐水 8 周,评估体重、食物摄入量、能量消耗、自发体力活动和血清瘦素水平。基于这第一个实验的结果,然后给予肥胖的 db/db 小鼠 NRG1 治疗 8 周。
与接受生理盐水治疗的小鼠相比,接受 NRG1 治疗的 C57BL/6JRJ 小鼠的血清瘦素浓度高 6 倍。与生理盐水治疗相比,NRG1 治疗还使体重增加减少了 10%,食物摄入量减少了 15%,而能量消耗保持不变。在 db/db 小鼠中,血清瘦素浓度、体重增加、食物摄入量、能量消耗和自发体力活动不受 NRG1 治疗的影响。
与 NRG1 治疗相关的 C57BL/6JRJ 小鼠的食物摄入量和体重增加减少可能部分归因于瘦素水平的增加,而 db/db 小鼠不受治疗的影响,表明在这种病理状态下对 NRG1 有抵抗作用。