男性雌性激素旺盛和肥胖（男性缺乏雌性激素）

一般的男性健身者对雌激素的认知主要在雌化、储水、拮抗睾酮等方面。虽然也隐约知道男性需要一些雌激素，但是大多数男性健身者一般还是认为男性要尽量减少雌激素水平。

其实雌激素对男性的作用很多，比如避免肥胖和保护肌肉。在中文互联网上，我还没有见过谁详细的写过这个话题，我们今天就专门讲下。

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一、雌激素有助于避免男性肥胖

肥胖是一种全球性的疾病，是一个越来越严重的公共卫生问题。全球超重和肥胖人口超过20亿，而且这个数字还在不断增加[1] [2] [3]。注意，肥胖与基因有很大的关系[4] [5] [6]，也跟激素有关。

人类是近20年才知道雌激素能保护男性、减少肥胖的。2006年，Jones等人首次发现并报道，男性如果缺乏雌激素，会导致肥胖[7]。

众所周知，女性体内的雌激素主要来自卵巢，而男性体内的雌激素仅有约15%来自睾丸[8]，而大部分主要来自芳香酶。芳香酶主要存在于脂肪组织中，负责将雄性激素转化为雌激素。

如果芳香酶的数量或者功能不正常，男性就无法获得足够的雌激素。Jones等人发现7名男性因为发生了CYP19基因的外显子突变，导致他们体内的芳香酶功能障碍，因此它们体内的雌激素水平低得几乎检测不到，而且他们的睾酮水平中等偏高。

图1

『雌激素水平极低、雄激素水平中等略高』，许多男网友可能觉得这是好事，因为他们都听说了『雌激素过多导致男性乳房发育、磁化、肥胖』的说法。

然而，体内雌激素水平极低的这7名男性身上有一大堆病，比骨骼发育迟缓、骨质酥松、肥胖、胰岛素抵抗，还有广大男同胞最不想发生的：生殖功能降低。

为了验证这个问题是否偶然，Jones等人进一步的观察，发现芳香酶基因敲除的雄性小鼠身上也观察到了相似的情况；通过这些观察他们证实，雌激素在调节哺乳动物的体重、肥胖和葡萄糖体内平衡中，发挥了关键性的保护作用。

甚至有些研究认为，雄性动物『缺乏雌激素』可能比『缺乏雄激素』更糟糕[9]，『缺乏雌激素』可导致雄性动物的体脂比其他正常雄性动物翻倍[10] [11]。

Heine等人用基因敲除技术制造了雌性激素受体敲除的雄性小鼠[12]（KO小鼠），这些小鼠体内能产生雌性激素，但它们所有的细胞上都没有雌激素受体，相当于变相失去了所有雌激素。

KO雄性小鼠随年龄增长体内的白色脂肪组织越来越多，到270-360日龄时，与正常小鼠相比，KO小鼠的附睾、肾脏周围和腹股沟的脂肪细胞增大20%、脂肪细胞数量增多82-168%、脂肪组织重量增多139%-185%。

图2：30和90日龄两组小鼠脂肪量对比

图3：180和270-360日龄两组小鼠脂肪量对比

值得一提的是，该研究中的普通雄性小鼠和KO雄性小鼠摄入的热量是一样的。

这句话让会让许多减肥只考虑总热量的人后背发凉，因为他们一直都是错的，他们一直以为减肥单纯就是吃和运动的的问题，就单纯只是总热量的问题。

图4

这是一个反驳『胖瘦只看总热量』的典型证据，在摄入热量一样的情况下，KO雄性小鼠比正常雄性小鼠胖多了（图4）。

它们摄入热量相同但却胖的多的原因不完全清楚，但研究者认为是ko雄性小鼠日常消耗的热量更少，大约少了11%（以及肌肉量减少）。

让雄性小鼠失去雌激素信号，除了敲除它们的雌激素受体基因，还可以敲除他们的芳香酶基因，因为雄性哺乳动物的大部分雌激素来自于脂肪细胞内的芳香酶。

脂肪细胞内的Cyp19基因编码出芳香酶，只要破坏了这个基因，小鼠就不能产生芳香酶[13]；Jones等人利用这种方式获得了芳香酶敲除小鼠（ArKO）[14]，它们基本不能合成内源性雌激素。

结果跟Heine等人[12]的研究相互支持，芳香酶敲除的小鼠（ArKO小鼠），不管雄性还是雌性，都变得更胖了。在1岁的年龄下，对于肾脏周围的脂肪积累（图5），ArKO雄性小鼠平均213.2g，普通小鼠平均105.8g，差距几乎一倍；

图5

性腺周围的脂肪细胞大小（图6），也是ArKO小鼠（B）明显比普通小鼠（A）更大；

图6

在全身脂肪总量方面（图7），ArKO小鼠（黑柱）明显比普通小鼠（白柱）更多，不管雄性和雌性都是如此；并且雄性ArKO小鼠的肥胖似乎比雌性更严重。

图7

对于肝脏的脂肪堆积（图8），ArKO小鼠明显比普通小鼠更严重；下图是对这些小鼠尸检的肝脏切片，肝细胞本身是恩红色，其中白色部分就是肝脏的脂肪堆积。

图8

对于ArKO小鼠肥胖的原因，作者强调：

excess body fat in the estrogen-insufficient ArKO mice was not due to hyperphagia or reduced resting energy expenditure, but was associated with decreased lean mass and reduced spontaneous physical activity.

雌激素不足的ArKO小鼠体内多余的脂肪，不是由于摄食过量导致的，而是因为瘦体重（肌肉组织减少）、静息能量消耗减低、身体活动减少造成的。

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二、雌激素通过中枢神经调节体重和能量代谢

文献表明，雌激素信号通过通过中枢神经机制[15] [16]。

下丘脑是食欲和能量消耗以及生殖行为的主要调节部位[17] [18]，下丘脑也有丰富的雌激素受体，特别是在弓状核、室旁核和腹内侧核[15] [19] [20]；而且，中枢神经系统中，如星型胶质细胞和神经元，具有将胆固醇合成雌激素所必须的酶[21]。

有趣的是，给雄性小鼠喂食大量的植物雌激素，尽管它们的食欲增加，但肥胖率却下降了[22]。

这可能是因为雌激素信号影响了下丘脑，比如Ogawa等人观察到切除睾丸后注射雌激素的雄性小鼠自主日常活动增加[23]（跑滚轮）——这与Heine等人[12]报告说雌激素不足的雄性小鼠瘦体重和身体活动减少相吻合。

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三、雌激素维持胰岛敏感性，保护骨骼肌

几乎所有人都知道雄性激素（睾酮类）对骨骼肌的重要保护作用。但是极少有网友知道雌激素也对肌肉具有保护作用，上面的许多研究中都提到了这一点。

首先是Jones等人[7]报道雌激素在调节哺乳动物的葡萄代谢中发挥了关键性的保护作用，然后Heine等人用基因敲除技术制造的雌性激素受体敲除的雄性小鼠[12]（KO小鼠）的血糖和血液胰岛素水平更高（图9）。

图9

消化过程中，食物（碳水化合物）从小肠以葡萄糖的形式吸收入血，再在胰岛素[24] [25]的帮助下进入各器官；胰岛素从血液到达肌细胞表面后[26]与受体结合[27] [28] [29] [30]，引发一系列细胞内的生物化学信号[31] [32]，促使葡萄糖转运蛋白往细胞表面移动，细胞摄取葡萄糖。

图10

如果骨骼肌发生了胰岛抵抗，血糖无法顺利进入骨骼肌，就会滞留在血液中，引起血糖升高；同时，身体会分泌更多的胰岛素来促进血糖进入骨骼肌（和其他器官）。所以血糖和血浆胰岛素都升高，就是胰岛抵抗的标志。

胰岛素的作用对增肌来说非常重要。

• 抗阻训练后的肌肉增长具有胰岛素依赖性，有足够胰岛素蛋白合成速率显著增加[33]；
• 使用抑制胰岛素分泌的药物，小鼠比目鱼肌、腓肠肌和肋上肌蛋白合成明显减少[34]；
• 使用抗胰岛素抗体，几乎完全阻断了氨基酸对肌蛋白质合成的刺激效果[35]；
• 胰岛素还能与氨基酸协同作用，产生1 1＞2的效果，放大蛋白质合成的效率[36][37]；
• 胰岛素通过刺激一氧化氮合成来扩张毛细血管[38]，肌细胞得到更多的血流量[39][40][41]和营养物质；
• 胰岛素抵抗则意味着肌细胞摄取的营养减少[42][43][44][45]；
• 2型肌纤维作为人体增肌的主力[46]，它以糖酵解为主要能量[46]。

胰岛抵抗是肌肉杀手。

胰岛抵抗是肌肉杀手。

胰岛抵抗是肌肉杀手。

重要的事说三遍。

回到本文，雌激素对男性（和女性）来说，具有维持胰岛敏感性、保护骨骼肌的作用，这解释了为什么绝经前的女性糖尿病发病率低于男性[53] [54]。

作为对比，喂食高脂肪饮食导致雄性动物的胰岛敏感性降低40-50%[55] [56]，但雌性动物和人类女性受益于雌激素的代谢保护作用，胰岛抵抗程度较少[57] [58] [59] [60]；在医学上也观察到，卵巢切除会损害肌肉葡萄糖摄取和储存，会导致肌肉减少[61] [62]。

雌激素对胰岛敏感性和肌肉的保护机制很复杂，而且是多样化的：

• 雌激素诱导AMPK激活[63][64]；
• 雌激素维持葡萄糖转运蛋白数量[65]（Glut4）；
• 雌激素促进Glut4在运动后数量上调[66][67]；
• 雌激素激活肌肉合成代谢信号（Akt信号）[68][69][70]；
• 雌激素通过FOXO1抑制肌肉分解的酶（泛素连接酶）[71]。

这些内容比较深，我们在本文就不铺开说了。

有趣的是，雌激素对男性（和女性）体脂的控制作用和肌肉的保护作用，可能解释了为什么女性热衷于减肥。雌激素对于女性肥胖具有抑制作用：失去雌激素的保护，雌性动物和人类绝经后，胰岛敏感性急剧下降、体脂和炎症水平增加[72] [73]。

所以，也许从潜意识里，女性对瘦的追求，其实是一种潜意识里对青春（雌激素控制体脂）的追求，或者说是挽留；她们希望通过运动减肥，把自己变成年轻时有丰富雌激素水平的苗条状态。

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