Kinzig Kimberly P, Hargrave Sara L, Tao Erin E
Ingestive Behavior Research Center, Department of Psychological Sciences, Purdue University, West Lafayette, IN 47907, USA.
Am J Physiol Endocrinol Metab. 2009 Feb;296(2):E282-90. doi: 10.1152/ajpendo.90523.2008. Epub 2008 Nov 18.
Previous studies have demonstrated that some endocrine consequences of long-term caloric restriction persist after weight restoration in human subjects. Here we evaluate effects of chronic food restriction in rats that were restricted to 70% of control kcal for 4 wk and subsequently weight restored. Measures were taken from rats at 80% (chronically restricted; CR), 90% (partially weight restored; PR), 100% (fully weight restored; FR), and after 4 wk at 100% body weight of controls (extended weight restored; ER). Plasma insulin and leptin were decreased, and ghrelin was increased in CR compared with controls. Leptin and ghrelin normalized with weight restoration at PR, FR, and ER; however, baseline insulin was not normalized until the ER state. Hypothalamic mRNA expression levels for proopiomelanocortin (POMC), agouti-related protein (AgRP), and neuropeptide Y (NPY) revealed significantly less POMC mRNA expression in CR and PR rats, and significantly less arcuate NPY mRNA in PR and FR. In the dorsomedial hypothalamus, CR, PR, and FR rats had significantly increased NPY expression that was not normalized until the ER state. In response to a test meal, insulin and ghrelin release patterns were altered through the FR stage, and ghrelin remained affected at ER. Collectively, these data demonstrate that mere weight restoration is not sufficient to normalize hypothalamic gene expression levels and endocrine responses to a meal, and that meal-related ghrelin responses persist despite weight restoration for up to 4 wk.
先前的研究表明，长期热量限制对人体产生的一些内分泌影响在体重恢复后仍然存在。在此，我们评估了对大鼠进行慢性食物限制的影响，这些大鼠被限制摄入相当于对照组70%的千卡热量，为期4周，随后体重恢复。在大鼠体重为对照组的80%（长期限制饮食；CR）、90%（部分体重恢复；PR）、100%（完全体重恢复；FR）时以及在达到对照组体重100% 4周后（延长体重恢复；ER）进行测量。与对照组相比，CR组大鼠的血浆胰岛素和瘦素水平降低，胃饥饿素水平升高。在PR、FR和ER阶段，随着体重恢复，瘦素和胃饥饿素水平恢复正常；然而，直到ER阶段，基础胰岛素水平才恢复正常。促肾上腺皮质激素原（POMC）、刺鼠相关蛋白（AgRP）和神经肽Y（NPY）的下丘脑mRNA表达水平显示，CR和PR组大鼠的POMC mRNA表达显著减少，PR和FR组大鼠的弓状核NPY mRNA显著减少。在背内侧下丘脑，CR、PR和FR组大鼠的NPY表达显著增加，直到ER阶段才恢复正常。在给予试验餐时，胰岛素和胃饥饿素的释放模式在FR阶段之前发生改变，并且在ER阶段胃饥饿素仍然受到影响。总体而言，这些数据表明，仅仅体重恢复不足以使下丘脑基因表达水平和对一餐的内分泌反应正常化，并且尽管体重恢复长达4周，但与进餐相关胃饥饿素反应仍然持续存在。
