Metabolic and Energetic Consequences of Fatherhood

描述（由申请人提供）：父亲身份可以影响男性的健康和寿命。这些影响背后的机制尚不清楚；然而，由于人类和其他哺乳动物的父亲经历了几种代谢重要激素的可预测变化，一种可能性是这些内分泌谱影响能量稳态、代谢和身体成分，进而影响健康和寿命。拟议的研究将描述加州小鼠（Peromyscus californicus）中父权的影响，这是一种一夫一妻制的啮齿动物，父亲在后代身上投入了大量资金，并在激素水平和体重方面发生了系统的变化。具体来说，本研究将测试父亲改变的假设：血浆代谢重要激素水平（目的1）；能量稳态、代谢、体重和体脂（目标2）；可能导致这些能量和代谢影响的行为（目标3）；父亲身份的这些后果是由父亲的胎次/年龄、子女的年龄和压力调节的。实验1将采用纵向设计来描述父亲身份对身体（体重、身体组成）、能量（静息和最大代谢率、每日能量消耗）、激素（皮质酮、睾酮）和行为（摄食行为、活动水平）测量的影响。数据将在五个时间点收集，跨度大约9个月，来自父亲（与配偶和幼崽住在一起）和非繁殖雄性（与卵巢切除的雌性住在一起）。每组中一半的老鼠将暴露在慢性间歇性噪音压力源中，另一半将保持在标准的实验室条件下。实验2将使用横断面方法进一步表征父亲身份对体重、身体成分和能量学预期影响的潜在激素、代谢和行为机制。具体来说，它将表征血液循环中

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.