胃饥饿素治疗可逆转胃切除小鼠体重增加和体脂减少的情况。
Ghrelin treatment reverses the reduction in weight gain and body fat in gastrectomised mice.
作者信息
Dornonville de la Cour C, Lindqvist A, Egecioglu E, Tung Y C L, Surve V, Ohlsson C, Jansson J-O, Erlanson-Albertsson C, Dickson S L, Håkanson R
机构信息
Department of Pharmacology, Institute of Physiological Sciences, University of Lund, BMC F13, S-221-84 Lund, Sweden.
出版信息
Gut. 2005 Jul;54(7):907-13. doi: 10.1136/gut.2004.058578. Epub 2005 Apr 21.
BACKGROUND AND AIMS
The gastric hormone ghrelin has been reported to stimulate food intake, increase weight gain, and cause obesity but its precise physiological role remains unclear. We investigated the long term effects of gastrectomy evoked ghrelin deficiency and of daily ghrelin injections on daily food intake, body weight, fat mass, lean body mass, and bone mass in mice.
METHODS
Ghrelin was given by subcutaneous injections (12 nmol/mouse once daily) for eight weeks to young female mice subjected to gastrectomy or sham operation one week previously.
RESULTS
Gastrectomy reduced plasma concentrations of total ghrelin (octanoylated and des-octanoylated) and active (octanoylated) ghrelin by approximately 80%. Immediately after injection of ghrelin, the plasma concentration was supraphysiological and was still elevated 16 hours later. Daily food intake was not affected by either gastrectomy or ghrelin treatment. The effect of ghrelin on meal initiation was not studied. At the end point of the study, mean body weight was 15% lower in gastrectomised mice than in sham operated mice (p<0.001); daily ghrelin injections for eight weeks partially prevented this weight loss. In sham operated mice, ghrelin had no effect on body weight. The weight of fat was reduced in gastrectomised mice (-30%; p<0.01). This effect was reversed by ghrelin, enhancing the weight of fat in sham operated mice also (+20%; p<0.05). Gastrectomy reduced lean body mass (-10%; p<0.01) and bone mass (-20%; p<0.001) compared with sham operated mice. Ghrelin replacement prevented the gastrectomy induced decrease in lean body mass but did not affect bone. In sham operated mice, ghrelin affected neither of these two parameters.
CONCLUSIONS
Ghrelin replacement partially reversed the gastrectomy induced reduction in body weight, lean body mass, and body fat but not in bone mass. In sham operated mice, ghrelin only increased fat mass. Our results suggest that ghrelin is mainly concerned with the control of fat metabolism and that ghrelin replacement therapy may alleviate the weight loss associated with gastrectomy.
背景与目的
胃激素ghrelin据报道可刺激食物摄入、增加体重并导致肥胖，但其确切的生理作用仍不清楚。我们研究了胃切除引起的ghrelin缺乏以及每日注射ghrelin对小鼠每日食物摄入量、体重、脂肪量、瘦体重和骨量的长期影响。
方法
对一周前接受胃切除术或假手术的年轻雌性小鼠，皮下注射ghrelin（12 nmol/只，每日一次），持续八周。
结果
胃切除术使总ghrelin（辛酰化和去辛酰化）和活性（辛酰化）ghrelin的血浆浓度降低了约80%。注射ghrelin后，血浆浓度立即超过生理水平，16小时后仍升高。每日食物摄入量不受胃切除术或ghrelin治疗的影响。未研究ghrelin对进餐起始的影响。在研究终点，胃切除小鼠的平均体重比假手术小鼠低15%（p<0.001）；每日注射ghrelin八周可部分预防这种体重减轻。在假手术小鼠中，ghrelin对体重无影响。胃切除小鼠的脂肪重量减少（-30%；p<0.01）。ghrelin可逆转这种作用，也使假手术小鼠的脂肪重量增加（+20%；p<0.05）。与假手术小鼠相比，胃切除术使瘦体重减少（-10%；p<0.01），骨量减少（-20%；p<0.001）。补充ghrelin可预防胃切除引起的瘦体重下降，但对骨量无影响。在假手术小鼠中，ghrelin对这两个参数均无影响。
结论
补充ghrelin可部分逆转胃切除引起的体重、瘦体重和体脂下降，但对骨量无影响。在假手术小鼠中，ghrelin仅增加脂肪量。我们的结果表明，ghrelin主要与脂肪代谢的控制有关，ghrelin替代疗法可能减轻与胃切除术相关的体重减轻。
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