17α-Estradiol Alleviates Age-related Metabolic and Inflammatory Dysfunction in Male Mice Without Inducing Feminization.
17α-Estradiol Alleviates Age-related Metabolic and Inflammatory Dysfunction in Male Mice Without Inducing Feminization.
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17α-雌二醇减轻雄性小鼠年龄相关的代谢和炎症功能障碍，而不会诱导女性化。
DOI：
10.1093/gerona/glv309
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发表时间：
2017-01
期刊：
影响因子：
--
通讯作者：
Kirkland JL
中科院分区：
文献类型：
--
作者：
Stout MB;Steyn FJ;Jurczak MJ;Camporez JG;Zhu Y;Hawse JR;Jurk D;Palmer AK;Xu M;Pirtskhalava T;Evans GL;de Souza Santos R;Frank AP;White TA;Monroe DG;Singh RJ;Casaclang-Verzosa G;Miller JD;Clegg DJ;LeBrasseur NK;von Zglinicki T;Shulman GI;Tchkonia T;Kirkland JL
衰老与内脏肥胖、代谢紊乱和慢性低度炎症有关。17α-雌二醇（17α-E2）是一种天然存在的17β-雌二醇（17β-E2）对映体，其延长雄性小鼠寿命的机制尚不清楚。我们测试了17α-E2是否可以缓解年龄相关性代谢功能障碍和炎症。17α-E2可降低体重、内脏脂肪和异位脂质沉积，但不降低瘦体重。这些下降与能量摄入减少有关，这是由于下丘脑缺氧途径的激活和17α-E2对内脏脂肪组织营养感应途径的直接影响。17α-E2不改变能量消耗和排泄。空腹血糖、胰岛素和糖化血红蛋白也被17α-E2降低，高胰岛素-正糖钳显示外周葡萄糖处理和肝脏葡萄糖生成的改善。17α-E2减少了内脏脂肪组织和循环中的炎症介质。17α-E2在内脏脂肪组织中增加AMPKα并降低mTOR复合物1活性，但在肝脏或股四头肌中没有，这与热量限制的全身效应相反。这些有益的表型变化发生在没有女性化或心功能障碍的情况下，这是外源性雌激素给药的两种常见有害影响。因此，17α-E2具有通过组织特异性作用减轻年龄相关代谢功能障碍的新疗法的潜力。
Aging is associated with visceral adiposity, metabolic disorders, and chronic low-grade inflammation. 17α-estradiol (17α-E2), a naturally occurring enantiomer of 17β-estradiol (17β-E2), extends life span in male mice through unresolved mechanisms. We tested whether 17α-E2 could alleviate age-related metabolic dysfunction and inflammation. 17α-E2 reduced body mass, visceral adiposity, and ectopic lipid deposition without decreasing lean mass. These declines were associated with reductions in energy intake due to the activation of hypothalamic anorexigenic pathways and direct effects of 17α-E2 on nutrient-sensing pathways in visceral adipose tissue. 17α-E2 did not alter energy expenditure or excretion. Fasting glucose, insulin, and glycosylated hemoglobin were also reduced by 17α-E2, and hyperinsulinemic-euglycemic clamps revealed improvements in peripheral glucose disposal and hepatic glucose production. Inflammatory mediators in visceral adipose tissue and the circulation were reduced by 17α-E2. 17α-E2 increased AMPKα and reduced mTOR complex 1 activity in visceral adipose tissue but not in liver or quadriceps muscle, which is in contrast to the generalized systemic effects of caloric restriction. These beneficial phenotypic changes occurred in the absence of feminization or cardiac dysfunction, two commonly observed deleterious effects of exogenous estrogen administration. Thus, 17α-E2 holds potential as a novel therapeutic for alleviating age-related metabolic dysfunction through tissue-specific effects.
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影响因子：
7.8
作者：
Harrison DE;Strong R;Allison DB;Ames BN;Astle CM;Atamna H;Fernandez E;Flurkey K;Javors MA;Nadon NL;Nelson JF;Pletcher S;Simpkins JW;Smith D;Wilkinson JE;Miller RA
通讯作者：
Miller RA
影响因子：
168.9
作者：
Christensen, Kaare;Doblhammer, Gabriele;Rau, Roland;Vaupel, James W.
通讯作者：
Vaupel, James W.
影响因子：
7.8
作者：
Akasaki Y;Ouchi N;Izumiya Y;Bernardo BL;Lebrasseur NK;Walsh K
通讯作者：
Walsh K
DOI：
10.1146/annurev-pathol-121808-102144
发表时间：
2010
期刊：
Annual review of pathology
影响因子：
--
作者：
Coppé JP;Desprez PY;Krtolica A;Campisi J
通讯作者：
Campisi J
影响因子：
64.5
作者：
Fontana L;Partridge L
通讯作者：
Partridge L