Laboratorio de Endocrinología Molecular y Celular, Instituto de Investigación Sanitaria de Santiago de Compostela, Complexo Hospitalario Universitario de Santiago (CHUS/SERGAS), Santiago de Compostela, Spain.
Peptides. 2010 Oct;31(10):1912-9. doi: 10.1016/j.peptides.2010.06.022. Epub 2010 Jun 30.
The aim of this research was to investigate the effect of long-term exposure to low leptin and high ghrelin levels, inherent to activity-based anorexia (ABA), on peripheral metabolism-implicated tissues such as muscle and fat depots. For this purpose, rats under ABA were submitted to a global study which included the characterization of body weight and composition change, the evaluation of leptin and ghrelin levels as well as their receptors expression at peripheral level. Our results confirm that feeding restriction to 1 h per day, and particularly the combination of this fasting regime with exercise (ABA), significantly reduces fat mass, decreases leptin circulating levels, increases ghrelin levels strikingly and enhances insulin sensitivity. By direct in vitro assays, we show that visceral and gonadal fat participate more than subcutaneous fat in the hypoleptinemia of these animals. The study of ghrelin (GHS-R1a) and leptin (LEPR) receptors at peripheral level exhibits a tissue-specific expression pattern. Concretely, oxidative-soleus type of muscle appears to be more susceptible to ghrelin and leptin circulating levels than glycolytic-gastrocnemius type under exercise and food restriction situations. In relation to adipose tissue, chronic hyperghrelinemia induces GHS-R1a expression on visceral and subcutaneous fat which might suggest the prevention of lipid loss. On the other hand, only subcutaneous fat express the active long form of LEPR compared to visceral and gonadal fat under low leptin levels in ABA animals. All together, these findings indicate tissue-specific mechanisms for the control of energy homeostasis in response to nutrient and energy availability.
本研究旨在探讨长期暴露于活动限制型厌食症（ABA）中固有低瘦素和高胃饥饿素水平对肌肉和脂肪等外周代谢组织的影响。为此，ABA 大鼠接受了一项全面研究，其中包括体重和组成变化的特征描述、外周瘦素和胃饥饿素水平及其受体表达的评估。我们的结果证实，每天限制进食 1 小时，特别是将这种禁食方案与运动（ABA）相结合，可显著减少脂肪量，降低循环瘦素水平，显著增加胃饥饿素水平，并提高胰岛素敏感性。通过直接的体外测定，我们表明内脏和性腺脂肪比皮下脂肪更多地参与了这些动物的低瘦素血症。外周瘦素（LEPR）和胃饥饿素（GHS-R1a）受体的研究表现出组织特异性表达模式。具体来说，在运动和食物限制的情况下，与糖酵解型比目鱼肌相比，氧化型比目鱼肌似乎对循环中的瘦素和胃饥饿素更为敏感。关于脂肪组织，慢性高胃饥饿素血症可诱导内脏和皮下脂肪中 GHS-R1a 的表达，这可能提示防止脂质流失。另一方面，在 ABA 动物低瘦素水平下，只有皮下脂肪表达 LEPR 的活性长形式，而内脏和性腺脂肪则不表达。总之，这些发现表明，在应对营养和能量供应时，存在针对能量平衡的组织特异性控制机制。
