Leone Sheila, Chiavaroli Annalisa, Shohreh Rugia, Ferrante Claudio, Ricciuti Adriana, Manippa Fabio, Recinella Lucia, Di Nisio Chiara, Orlando Giustino, Salvatori Roberto, Vacca Michele, Brunetti Luigi
Department of Pharmacy, G. d'Annunzio University, Chieti, Italy.
Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Growth Horm IGF Res. 2015 Apr;25(2):80-4. doi: 10.1016/j.ghir.2014.12.007. Epub 2015 Jan 2.
Growth hormone (GH) deficiency (GHD) leads to growth failure and changes in body composition, including increased fat accumulation and reduced lean body mass in both humans and rodents. The aim of this study was to examine the factors that contribute to energy imbalance in the GH releasing hormone knock out (GHRHKO) mice, a well established model of GHD.
We evaluated food intake (of standard laboratory chow), total body weight (TBW), locomotor activity, body temperature and interscapular brown adipose tissue (BAT) weight in 8 adult male mice homozygous for the GHRHKO allele (-/-) and 8 heterozygous (+/-) animals as controls. The gene expression of uncoupling protein-1 (UCP-1) in BAT and the levels of norepinephrine (NE), dopamine (DA), and serotonin (5-hydroxytryptamine, 5-HT) in the ventral striatum were measured by real-time reverse transcription polymerase chain reaction (RT-PCR) and high performance liquid chromatography (HPLC) analysis, respectively.
Throughout 2 months of observation -/- mice consumed approximately 40% more food (normalized to TBW; P<0.001), and showed increased locomotor activity in 24h time compared to controls (P<0.05). Moreover, -/- animals showed increased body temperature (P<0.001), BAT weight (P<0.001), and UCP-1 gene expression (P<0.001), while NE levels in the striatum area were lower (P<0.05) than controls.
The present study demonstrates that the increased food intake observed in GHRH ablated animals is associated with increased locomotor and thermogenic activity.
生长激素（GH）缺乏（GHD）会导致生长发育迟缓以及身体成分改变，包括人类和啮齿动物体内脂肪堆积增加和瘦体重减少。本研究旨在探讨导致生长激素释放激素基因敲除（GHRHKO）小鼠能量失衡的因素，该小鼠是一种成熟的GHD模型。
我们评估了8只纯合GHRHKO等位基因（-/-）的成年雄性小鼠和8只作为对照的杂合子（+/-）动物的食物摄入量（标准实验室饲料）、总体重（TBW）、运动活动、体温和肩胛间棕色脂肪组织（BAT）重量。分别通过实时逆转录聚合酶链反应（RT-PCR）和高效液相色谱（HPLC）分析测量BAT中解偶联蛋白-1（UCP-1）的基因表达以及腹侧纹状体中去甲肾上腺素（NE）、多巴胺（DA）和5-羟色胺（5-HT）的水平。
在整个2个月的观察期内，与对照组相比，-/-小鼠的食物摄入量（以TBW标准化；P<0.001）多约40%，并且在24小时内的运动活动增加（P<0.05）。此外，-/-动物的体温升高（P<0.001）、BAT重量增加（P<0.001）以及UCP-1基因表达增加（P<0.001），而纹状体区域的NE水平低于对照组（P<0.05）。
本研究表明，在GHRH缺失的动物中观察到的食物摄入量增加与运动和产热活动增加有关。
