Wortley Katherine E, Garcia Karen, Okamoto Haruka, Thabet Karen, Anderson Keith D, Shen Victor, Herman Jim P, Valenzuela David, Yancopoulos George D, Tschöp Matthias H, Murphy Andrew, Sleeman Mark W
Regeneron Pharmaceuticals Inc, Tarrytown, New York, USA.
Gastroenterology. 2007 Nov;133(5):1534-43. doi: 10.1053/j.gastro.2007.08.024. Epub 2007 Aug 15.
BACKGROUND & AIMS: Peptide YY (PYY) and pancreatic polypeptide (PPY) are members of the neuropeptide Y peptide family. The neuropeptide Y receptor signaling pathway has been implicated in a number of physiologic processes, including the regulation of energy balance and bone mass. To investigate the contribution of endogenous PYY and PPY to these processes, we generated both Pyy- and Ppy-deficient mice.
Pyy(-/-) and Ppy(-/-) mice and their respective wild-type littermates were studied from 8 weeks to 9 months of age. Food intake, metabolic parameters, and locomotor activity were monitored using indirect calorimetry. Body composition and bone parameters were analyzed using dual energy x-ray absorptiometry, histomorphometry, and vertebral compression testing.
Studies in these mice showed an osteopenic phenotype specific to the Pyy-deficient line, which included a reduction in trabecular bone mass and a functional deficit in bone strength. Furthermore, female Pyy(-/-) mice showed a greater sensitivity to ovariectomy-induced bone loss compared with wild-type littermates. No food intake or metabolic phenotype was apparent in male or female Pyy(-/-) mice on standard chow. However, female Pyy(-/-) mice on a high-fat diet showed a greater propensity to gain body weight and adiposity. No metabolic or osteopenic phenotype was observed in Ppy-deficient mice.
These results indicate that endogenous PYY plays a critical role in regulating bone mass. In comparison, its role in regulating body weight is minor and is confined to situations of high-fat feeding.
肽YY(PYY)和胰多肽(PPY)是神经肽Y肽家族的成员。神经肽Y受体信号通路参与了许多生理过程,包括能量平衡和骨量的调节。为了研究内源性PYY和PPY对这些过程的作用,我们培育了PYY和PPY基因敲除小鼠。
对8周龄至9月龄的PYY基因敲除小鼠、PPY基因敲除小鼠及其各自的野生型同窝小鼠进行研究。使用间接量热法监测食物摄入量、代谢参数和运动活性。使用双能X线吸收法、组织形态计量学和椎体压缩试验分析身体组成和骨参数。
对这些小鼠的研究显示,PYY基因敲除品系存在特定的骨质减少表型,包括小梁骨量减少和骨强度功能缺陷。此外,与野生型同窝小鼠相比,雌性PYY基因敲除小鼠对卵巢切除诱导的骨质流失更为敏感。标准饲料喂养的雄性或雌性PYY基因敲除小鼠未出现明显的食物摄入或代谢表型。然而,高脂饮食的雌性PYY基因敲除小鼠体重增加和肥胖的倾向更大。PPY基因敲除小鼠未观察到代谢或骨质减少表型。
这些结果表明,内源性PYY在调节骨量中起关键作用。相比之下,其在调节体重方面的作用较小,且仅限于高脂喂养的情况。