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解偶联蛋白2和3随年龄的变化:禁食和β3-肾上腺素能激动剂治疗的调节作用

Uncoupling proteins 2 and 3 with age: regulation by fasting and beta3-adrenergic agonist treatment.

作者信息

Scarpace P J, Kumar M V, Li H, Tümer N

机构信息

Geriatric Research, Education and Clinical Center, Malcom Randall Department of Veterans Affairs Medical Center, Gainesville, Florida 32608-1197, USA.

出版信息

J Gerontol A Biol Sci Med Sci. 2000 Dec;55(12):B588-92. doi: 10.1093/gerona/55.12.b588.

DOI:10.1093/gerona/55.12.b588
PMID:11129388
Abstract

In rodents, adaptive thermogenesis in brown adipose tissue (BAT) serves both to regulate body mass after hyperphagia and to conserve energy during food deprivation. In addition to uncoupling protein 1 (UCP1), UCP3 and possibly UCP2 may have a role in energy homeostasis in BAT. We examined basal levels of UCP2 and UCP3 mRNA with age and regulation of UCP1, UCP2, and UCP3 mRNA by two conditions known to modulate energy homeostasis: fasting and beta3-adrenergic agonists. UCP1, UCP2, and UCP3 mRNA levels were unchanged between 3, 24, and 31 months of age in BAT, and UCP2 and UCP3 mRNA levels were unchanged between 6 and 24 months of age in retroperitoneal white adipose tissue (RTWAT). Following a 2-day fast, there were sizable reductions in BAT UCP1 and UCP3 mRNA, but these decreases with fasting were significantly less in the older compared with the young rats. Fasting had no effect on UCP2 mRNA levels at any age. The beta3-adrenergic agonist, CL316,243, increased BAT UCP1 and UCP3 mRNA equally in both young and old rats. The beta3-adrenergic agonist did not increase UCP2 mRNA in BAT but did increase expression in RTWAT of both young and old rats. In summary, these data indicate that the expression of the three uncoupling proteins is unchanged with age. Although the upregulation of these uncoupling proteins by beta3-adrenergic agonist treatment is maintained with age, the downregulation by fasting is diminished with age. The parallel regulation of UCP1 and UCP3 expression in BAT suggests that UCP3, like UCP1, may have a role in energy homeostasis in BAT. The diminished downregulation of UCP1 and UCP3 expression in BAT by fasting suggests that energy conservation in response to food deprivation is impaired with age, and this may contribute to an inability of older animals to maintain body mass during periods when food is limited.

摘要

在啮齿动物中,棕色脂肪组织(BAT)中的适应性产热作用在于在摄食过多后调节体重以及在食物缺乏时保存能量。除了解偶联蛋白1(UCP1)外,UCP3以及可能的UCP2可能在BAT的能量稳态中发挥作用。我们研究了UCP2和UCP3 mRNA的基础水平随年龄的变化情况,以及已知可调节能量稳态的两种条件(禁食和β3 - 肾上腺素能激动剂)对UCP1、UCP2和UCP3 mRNA的调节作用。BAT中UCP1、UCP2和UCP3 mRNA水平在3、24和31月龄时未发生变化,腹膜后白色脂肪组织(RTWAT)中UCP2和UCP3 mRNA水平在6和24月龄时未发生变化。禁食2天后,BAT中UCP1和UCP3 mRNA有显著降低,但与年轻大鼠相比,老年大鼠禁食后的这些降低幅度明显较小。禁食在任何年龄对UCP2 mRNA水平均无影响。β3 - 肾上腺素能激动剂CL316,243在年轻和老年大鼠中均同等程度地增加了BAT中UCP1和UCP3 mRNA。β3 - 肾上腺素能激动剂未增加BAT中UCP2 mRNA,但增加了年轻和老年大鼠RTWAT中的表达。总之,这些数据表明三种解偶联蛋白的表达随年龄未发生变化。尽管β3 - 肾上腺素能激动剂处理对这些解偶联蛋白的上调作用随年龄保持不变,但禁食导致的下调作用随年龄减弱。BAT中UCP1和UCP3表达的平行调节表明,UCP3与UCP1一样,可能在BAT的能量稳态中发挥作用。BAT中UCP1和UCP3表达因禁食导致的下调作用减弱表明,随着年龄增长,对食物缺乏做出的能量保存反应受损,这可能导致老年动物在食物有限的时期无法维持体重。

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