Matsumoto A M, Marck B T, Gruenewald D A, Wolden-Hanson T, Naai M A
Geriatric Research, Education and Clinical Center, V.A. Puget Sound Health Care System, 1660 South Columbian Way (S-182-GRECC), Seattle, WA 98108-1597, USA.
Exp Gerontol. 2000 Dec;35(9-10):1251-65. doi: 10.1016/s0531-5565(00)00158-3.
Aging in men is associated with a decline in trophic factors such as testosterone (T), alterations in body composition and impaired energy and body weight regulation. We performed studies to investigate the mechanisms underlying age-related changes in the neuroendocrine control of testis function, body composition, food intake and body weight in the Brown Norway (BN) rat. We found that similar to aging men, male BN rats demonstrate both primary and secondary testicular failure with aging without confounding age-related tumors, hormonal changes and systemic illnesses. With aging, these animals have blunted circadian variations in luteinizing hormone (LH) and T, and decreased hypothalamic gonadotropin-releasing hormone (GnRH) synthetic capacity with preserved pituitary gonadotropin responses to GnRH. We found that aging male BN rats have increased peripheral and visceral adiposity associated with increased insulin and leptin levels, and decreased relative lean body mass and muscle mass. We found that these rats exhibit reduced food intake and body weight gain associated with decreased hypothalamic neuropeptide Y (NPY) gene expression in the arcuate nucleus (ARC), both during ad-libitum feeding and after a 72-h fast. Recently, we found that old male BN rats treated chronically with troglitazone, an insulin sensitizer, lowered high insulin and leptin levels, decreased body fat, and corrected the blunted food intake and body weight gain response to fasting without affecting basal ARC NPY gene expression. These findings suggested that hyperinsulinemia and/or hyperleptinemia associated with aging may contribute to the age-related impairment in energy and weight regulation. Our studies suggest that the aging male BN rat is an excellent model to investigate the mechanisms underlying the age-associated changes in the neuroendocrine control of body composition, energy intake and body weight.
男性衰老与诸如睾酮（T）等营养因子水平下降、身体成分改变以及能量和体重调节受损有关。我们开展了研究，以探究棕色挪威（BN）大鼠睾丸功能、身体成分、食物摄入和体重的神经内分泌控制方面与年龄相关变化的潜在机制。我们发现，与衰老男性相似，雄性BN大鼠随着年龄增长会出现原发性和继发性睾丸功能衰竭，且不存在与年龄相关的肿瘤、激素变化和全身性疾病的干扰。随着年龄增长，这些动物的促黄体生成素（LH）和T的昼夜节律变化减弱，下丘脑促性腺激素释放激素（GnRH）合成能力下降，而垂体促性腺激素对GnRH的反应保持不变。我们发现，衰老的雄性BN大鼠外周和内脏脂肪增多，同时胰岛素和瘦素水平升高，相对瘦体重和肌肉量减少。我们发现，无论是在随意进食期间还是在禁食72小时后，这些大鼠的食物摄入量和体重增加均减少，这与弓状核（ARC）中下丘脑神经肽Y（NPY）基因表达降低有关。最近，我们发现长期用胰岛素增敏剂曲格列酮治疗的老年雄性BN大鼠，其高胰岛素和瘦素水平降低，体脂减少，并且纠正了对禁食的食物摄入量和体重增加反应减弱的情况，而不影响ARC基础NPY基因表达。这些发现表明，与衰老相关的高胰岛素血症和/或高瘦素血症可能导致能量和体重调节方面与年龄相关的损害。我们的研究表明，衰老的雄性BN大鼠是研究身体成分、能量摄入和体重的神经内分泌控制中与年龄相关变化的潜在机制的极佳模型。
