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父亲在几种重要的代谢激素中发生了可预测的变化，一种可能性是这些内分泌特征影响能量稳态，代谢和身体组成，这反过来又会影响健康和长寿。拟议中的研究将描述加州小鼠（Peromyscus californicus）中父亲身份的影响，这是一种单配偶制啮齿动物，父亲在后代身上投入大量资金，并在激素水平和体重方面发生系统性变化。具体来说，本研究将测试的假设，父亲改变：血浆水平的代谢重要的激素（目标1）;能量稳态，代谢，体重和体脂（目标2）;行为，可能有助于这些能量和代谢的影响（目标3）;和这些后果的父亲是由父亲的奇偶校验/年龄，后代年龄和压力调制。实验1将采用纵向设计来表征父亲身份对身体（体重，身体成分），精力充沛（休息和最大代谢率，每日能量消耗），激素（皮质酮，睾酮）和行为（摄食行为，活动水平）措施的影响。将在5个时间点收集数据，时间跨度约为9个月，来自父亲（与配偶和幼仔一起饲养）和非繁殖雄性（与卵巢切除雌性动物一起饲养）。每组中的一半小鼠将暴露于慢性间歇性噪声应激源，另一半将保持在标准实验室条件下。实验2将使用横截面的方法，以进一步表征可能的激素，代谢和行为机制的预期影响的父亲对身体质量，身体成分和精力。具体而言，它将表征1）循环水平 代谢激素瘦素、脂联素、三碘甲状腺原氨酸和甲状腺素; 2）血液甘油三酯， 胆固醇和葡萄糖水平; 3）摄入高脂肪和高蔗糖物质的倾向; 4）非繁殖雄性、新父亲和有经验父亲的器官质量和脂肪储存分布。根据实验1的结果，每组中一半的小鼠可能再次暴露于慢性间歇性噪声应激源。这些研究预计将证明，在P. californicus的父亲改变代谢激素水平，能量稳态，新陈代谢，身体组成和行为。他们还将阐明这些影响是如何通过父亲年龄/产次，后代年龄和慢性压力来调节的。这些结果将为哺乳动物父性的生物学提供独特的见解，并可能最终导致更好地了解父性对男性健康和寿命的影响，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.