Darcy Justin, McFadden Samuel, Fang Yimin, Berryman Darlene E, List Edward O, Milcik Nicholas, Bartke Andrzej
Division of Geriatric Research, Department of Internal Medicine, Southern Illinois University School of Medicine, Springfield, IL 62702, USA.
Department of Medical Microbiology, Immunology and Cell Biology, Southern Illinois University School of Medicine, Springfield, IL 62702, USA.
Aging (Albany NY). 2018 Oct 18;10(10):2709-2722. doi: 10.18632/aging.101582.
Ames dwarf () mice possess a loss-of-function mutation that results in deficiency of growth hormone, prolactin, and thyroid-stimulating hormone, as well as exceptional longevity. Work in other laboratories suggests that increased respiration and lipid utilization are important for maximizing mammalian longevity. Interestingly, these phenotypes are observed in Ames dwarf mice. We recently demonstrated that Ames dwarf mice have hyperactive brown adipose tissue (BAT), and hypothesized that this may in part be due to their increased surface to mass ratio leading to increased heat loss and an increased demand for thermogenesis. Here, we used increased environmental temperature (eT) to interrogate this hypothesis. We found that increased eT diminished BAT activity in Ames dwarf mice, and led to the normalization of both VO and respiratory quotient between dwarf and normal mice, as well as partial normalization (i.e. impairment) of glucose homeostasis in Ames dwarf mice housed at an increased eT. Together, these data suggest that an increased demand for thermogenesis is partially responsible for the improved energy metabolism and glucose homeostasis which are observed in Ames dwarf mice.
艾姆斯侏儒(Ames dwarf)小鼠存在功能丧失性突变,导致生长激素、催乳素和促甲状腺激素缺乏,同时具有超长寿命。其他实验室的研究表明,呼吸增加和脂质利用对最大化哺乳动物寿命很重要。有趣的是,这些表型在艾姆斯侏儒小鼠中也有观察到。我们最近证明,艾姆斯侏儒小鼠的棕色脂肪组织(BAT)过度活跃,并推测这可能部分归因于它们增加的表面积与质量比,导致热量损失增加以及对产热的需求增加。在此,我们利用环境温度升高(eT)来验证这一假设。我们发现,环境温度升高会降低艾姆斯侏儒小鼠的棕色脂肪组织活性,并使侏儒小鼠和正常小鼠之间的耗氧量(VO)和呼吸商正常化,同时,在环境温度升高的条件下饲养的艾姆斯侏儒小鼠的葡萄糖稳态也会部分恢复正常(即受损)。总之,这些数据表明,产热需求增加部分导致了艾姆斯侏儒小鼠中观察到的能量代谢改善和葡萄糖稳态。