Darcy Justin, McFadden Samuel, Fang Yimin, Huber Joshua A, Zhang Chi, Sun Liou Y, Bartke Andrzej
Department of Internal Medicine (J.D., S.M., Y.F., J.A.H., C.Z., A.B.), Geriatric Research, and Department of Medical Microbiology, Immunology, and Cell Biology (J.D., A.B.), Southern Illinois University School of Medicine, Springfield, Illinois 62702; Institute of Cardiovascular Disease (C.Z.), Key Laboratory for Arteriosclerology of Hunan Province, University of South China, Hengyang 421001, People's Republic of China; and Department of Biology (L.Y.S.), University of Alabama at Birmingham, Birmingham, Alabama 35294.
Endocrinology. 2016 Dec;157(12):4744-4753. doi: 10.1210/en.2016-1593. Epub 2016 Oct 14.
Ames dwarf mice (Prop1) are long-lived due to a loss of function mutation, resulting in deficiency of GH, TSH, and prolactin. Along with a marked extension of longevity, Ames dwarf mice have improved energy metabolism as measured by an increase in their oxygen consumption and heat production, as well as a decrease in their respiratory quotient. Along with alterations in energy metabolism, Ames dwarf mice have a lower core body temperature. Moreover, Ames dwarf mice have functionally altered epididymal white adipose tissue (WAT) that improves, rather than impairs, their insulin sensitivity due to a shift from pro- to anti-inflammatory cytokine secretion. Given the unique phenotype of Ames dwarf epididymal WAT, their improved energy metabolism, and lower core body temperature, we hypothesized that Ames dwarf brown adipose tissue (BAT) may function differently from that of their normal littermates. Here we use histology and RT-PCR to demonstrate that Ames dwarf mice have enhanced BAT function. We also use interscapular BAT removal to demonstrate that BAT is necessary for Ames dwarf energy metabolism and thermogenesis, whereas it is less important for their normal littermates. Furthermore, we show that Ames dwarf mice are able to compensate for loss of interscapular BAT by using their WAT depots as an energy source. These findings demonstrate enhanced BAT function in animals with GH and thyroid hormone deficiencies, chronic reduction of body temperature, and remarkably extended longevity.
艾姆斯侏儒小鼠（Prop1）由于功能丧失突变而寿命延长，导致生长激素（GH）、促甲状腺激素（TSH）和催乳素缺乏。除了显著延长寿命外，艾姆斯侏儒小鼠的能量代谢也有所改善，表现为耗氧量和产热增加，呼吸商降低。随着能量代谢的改变，艾姆斯侏儒小鼠的核心体温较低。此外，艾姆斯侏儒小鼠附睾白色脂肪组织（WAT）的功能发生改变，由于促炎细胞因子分泌向抗炎细胞因子分泌的转变，其胰岛素敏感性得到改善而非受损。鉴于艾姆斯侏儒附睾WAT的独特表型、其改善的能量代谢和较低的核心体温，我们推测艾姆斯侏儒棕色脂肪组织（BAT）的功能可能与其正常同窝小鼠不同。在此，我们使用组织学和逆转录聚合酶链反应（RT-PCR）来证明艾姆斯侏儒小鼠的BAT功能增强。我们还通过切除肩胛间BAT来证明，BAT对艾姆斯侏儒小鼠的能量代谢和产热是必需的，而对其正常同窝小鼠则不太重要。此外，我们表明艾姆斯侏儒小鼠能够通过将其WAT储存作为能量来源来补偿肩胛间BAT的缺失。这些发现表明，在生长激素和甲状腺激素缺乏、体温长期降低且寿命显著延长的动物中，BAT功能增强。
