Metabolic and Energetic Consequences of Fatherhood

描述(申请人提供)：为人父会影响男性的健康和长寿。这些影响的机制尚不清楚；然而，由于人类和其他哺乳动物的父亲在几种代谢重要荷尔蒙中经历了可预见的变化，一种可能性是，这些内分泌特征影响能量平衡、新陈代谢和身体组成，进而可能影响健康和寿命。这项拟议的研究将描述加州小鼠(Permyscus CalforNicus)为父的影响，这是一种一夫一妻制的啮齿动物，父亲在后代身上进行广泛投资，并在激素水平和体重方面进行系统性变化。具体地说，这项研究将测试父亲改变的假设：代谢重要荷尔蒙的血浆水平(目标1)；能量平衡、新陈代谢、体重和体脂(目标2)；可能有助于这些能量和代谢效应的行为(目标3)；以及父亲的这些后果受父亲的胎次/年龄、后代年龄和压力的调节。实验1将使用纵向设计来描述父亲对身体(体重、身体成分)、能量(休息和最大代谢率、每日能量消耗)、荷尔蒙(皮质酮、睾酮)和行为(摄取行为、活动水平)测量的影响。数据将在五个时间点收集，时间跨度约为9个月，分别来自父亲(与配偶和幼崽一起居住)和不生育的雄性(与卵巢切除的雌性居住)。每组中一半的小鼠将暴露在慢性、间歇性噪音应激源中，另一半将在标准的实验室条件下保持。实验2将使用横断面方法进一步表征可能的荷尔蒙、代谢和行为机制，这些机制是父亲对身体质量、身体成分和能量的预期影响的基础。具体地说，它将表征1)循环水平 代谢激素瘦素、脂联素、三碘甲腺原氨酸和甲状腺素；2)血甘油三酯， 胆固醇和血糖水平；3)摄入高脂肪和高蔗糖物质的倾向；以及4)器官质量和脂肪储存的分布，在没有生育能力的男性、初为父亲的和有经验的父亲中。根据实验1的结果，每组中有一半的小鼠可能再次暴露在慢性、间歇性噪音应激源中。这些研究有望证明加州拟青蟹为父会改变新陈代谢激素水平、能量平衡、新陈代谢、身体成分和行为。他们还将阐明这些影响是如何受到父亲的年龄/产次、子女年龄和慢性压力的影响的。这些结果将为哺乳动物为父的生物学提供独特的见解，并最终可能有助于更好地理解父亲对男性健康和长寿的影响，以及他们后代的健康结果。

DESCRIPTION (provided by applicant): Fatherhood can influence health and longevity in men. The mechanisms underlying these effects are unknown; however, as human and other mammalian fathers undergo predictable changes in several metabolically important hormones, one possibility is that these endocrine profiles influence energy homeostasis, metabolism, and body composition, which in turn can affect health and longevity. The proposed studies will characterize the effects of fatherhood in the California mouse (Peromyscus californicus), a monogamous rodent in which fathers invest extensively in their offspring and undergo systematic changes in hormone levels and body mass. Specifically, this research will test the hypotheses that fatherhood alters: plasma levels of metabolically important hormones (Aim 1); energy homeostasis, metabolism, body mass, and body fat (Aim 2); behaviors that may contribute to these energetic and metabolic effects (Aim 3); and that these consequences of fatherhood are modulated by paternal parity/age, offspring age, and stress. Experiment 1 will use a longitudinal design to characterize the effects of fatherhood on physical (body mass, body composition), energetic (resting and maximal metabolic rates, daily energy expenditure), hormonal (corticosterone, testosterone), and behavioral (ingestive behavior, activity levels) measures. Data will be collected at five time points, spanning approximately a 9-month period, from fathers (housed with a mate and pups) and nonbreeding males (housed with an ovariectomized female). Half of the mice in each group will be exposed to a chronic, intermittent noise stressor, and the other half will be maintained under standard laboratory conditions. Experiment 2 will use a cross-sectional approach to further characterize possible hormonal, metabolic, and behavioral mechanisms underlying the anticipated effects of fatherhood on body mass, body composition, and energetics. Specifically, it will characterize 1) circulating levels of the metabolic hormones leptin, adiponectin, triiodothyronine, and thyroxine; 2) blood triglyceride, cholesterol, and glucose levels; 3) the propensity to ingest high-fat and high-sucrose substances; and 4) organ masses and distribution of fat stores, in nonbreeding males, new fathers, and experienced fathers. Depending on the results of Experiment 1, half of the mice in each group may again be exposed to a chronic, intermittent noise stressor. These studies are expected to demonstrate that fatherhood in P. californicus alters metabolic hormone levels, energy homeostasis, metabolism, body composition, and behavior. They will also clarify how these effects are modulated by paternal age/parity, offspring age, and chronic stress. The results will provide unique insights into the biology of mammalian fatherhood and may eventually lead to an improved understanding of the effects of fatherhood on health and longevity in men, as well as health outcomes in their offspring.