為什麼面對食物總是難禁誘惑？是意志力的缺失還是吃貨的扭曲？現在科學證明，你可以放過食物放過自己了，你可能只是身體的白素太多而已。愛吃是人的天性，想要控制住嘴巴，不是一個與食物作戰的過程，而是一個與自身激素作戰的過程。
▲《美國醫學雜誌》2017/11/06期
➊白素：第二個刺激食慾的外周激素
在2017年11月6號的《自然醫學》雜誌上，兩個中國醫學團隊合作發現，白素（Asprosin）是一個可以穿過血腦屏障，作用於大腦中關鍵的AgRP神經元，刺激食慾維持體重的激素。這項發現有望給糖尿病、肥胖和厭食症帶來新療法。
“Asprosin is a recently discovered fasting-induced hormone that promotes hepatic glucose production. Here we demonstrate that asprosin in the circulation crosses the blood–brain barrier and directly activates orexigenic AgRP+ neurons via a cAMP-dependent pathway. This signaling results in inhibition of downstream anorexigenic proopiomelanocortin (POMC)-positive neurons in a GABA-dependent manner, which then leads to appetite stimulation and a drive to accumulate adiposity and body weight.”——Nature Medicine
說到了AgRP神經元，那就不得提POMC神經元，畢竟它們是一對控制食慾的關鍵神經元，一個刺激食慾，一個抑制食慾。讓研究人員發現，34nmol的白素可以抑制85%的POMC神經元。
根據徐勇教授的透露，他們在有限的小鼠樣本里發現，正常的白素水平在5-25nmol，而肥胖的人群和小鼠都會增加2倍左右。所以，對於肥胖患者來說，過高的白素水平很可能過度激活AgRP神經元，又大量抑制POMC神經元，讓他們總想吃東西，根本停不下來。
“we found that immunological neutralization of asprosin reduced baseline AgRP+ neuron activity and resulted in a reduction in daily food intake. We extended those findings to obesity by demonstrating that chronic immunologic neutralization of asprosin in two independent mouse models of obesity (HFD-induced obesity and Leprdb/db mutation) resulted in a reduction in daily food intake along with a reduction in body weight. Of note, the absence of leptin signaling in the setting of the Leprdb/db mutation did not affect the result, suggesting distinct mechanisms of action for asprosin and leptin in AgRP+ and POMC+ neurons.”——Nature
➋抑制白素水平減少食慾
既然白素可以作用於神經元促進食慾，增加攝食導致肥胖，如果能夠抑制白素的水平，是不是就可以幫忙「減肥」呢？為了驗證這一點，研究人員使用靶向白素的單抗進行了小鼠實驗。在實驗中，經過一夜的禁食，正常小鼠的AgRP神經元非常活躍，它們「嗷嗷待哺」，但是改造後的小鼠對此“無動於衷”，禁食並沒有激活它們的AgRP神經元，產生飢餓感和食慾。而研究人員給小鼠額外補充了白素後，小鼠的AgRP神經元可以被正常激活，食量也隨之恢復了正常。
“We placed Fbn1NPS/+ mice and WT littermate controls on a HFD for 3 months and found a widening difference in body weight and fat mass between the two groups. On normal chow, the body weight curves of Fbn1NPS/+ mice were already markedly different from those of WT mice at weaning age (3 weeks old), culminating in a 10-g weight difference between the groups at 10 weeks of age. We exposed mice to severe diabetogenic and obesogenic stress (HFD for 6 months; 60% calories from fat) and found that, as compared with WT mice, Fbn1NPS/+ mice were completely protected from both obesity and diabetes (Supplementary Fig. 1c–e).”
在實驗過程中，他們發現了一個意外的現象：在60%能量都來自脂肪的高脂飲食餵養的小鼠組，這些小鼠依然沒有像普通小鼠那樣變得肥胖、患上糖尿病.既然白素可以通過激活AgRP神經元，刺激食慾，那麼AgRP是一個必要條件嗎？研究人員再次進行了實驗驗證。結果顯示，小鼠失去了AgRP神經元后，用普通飲食餵養，白素介導的食慾完全消失了！此外，他們在肥胖的人和小鼠中都觀察到了白素水平的病理性升高，當給肥胖小鼠使用抑制白素水平的單抗後，小鼠成功“減肥”了！
“Sandwich ELISA was used to measure plasma asprosin levels in male WT mice that had been subjected to a high-fat diet (60% of calories from fat) or normal chow for 12 weeks and from 5-week-old male Ob/+ or Ob/Ob mice upon 2 hr of fasting for synchronization (n = 5 mice in each group).”
➌高脂飲食可以繞開食慾激素影響
不過有意思的是，換成了高脂飲食後，這些小鼠對白素的應答竟然恢復了部分，看來，高脂飲食（High-fat diet）厲害啊，還可以在食慾激素受限的情況下，激活別的神經元去產生食慾呢。也就是說，高脂飲食可以避開外周激素的影響，不管白素是否分泌，既不會在激素分泌過少的時候減少食慾，也不會在食慾增加時引發糖尿病和肥胖，可以說是相當環保地讓身體維持在一個健康穩定的狀態。
“Similar to that seen in the human disorder, within the context of thinness, Fbn1NPS/+ mice displayed hypophagia along with a likely compensator y reduction in energy expenditure. Energy expenditure was also assessed using analysis of covariance (ANCOVA) to avoid the confounding effects of preexisting low body weight and lean mass in Fbn1NPS/+ mice, allowing for adjustment of the covariates.”
減肥教有話說
在以白素為靶點的「減肥藥」研發出來之前，我們只能選擇「曲線救國」了。比起不吃少吃，靠意志力與自身的食慾激素博弈，更科學的方法是懂得怎樣吃。我們倡導LCHF「低糖優脂」飲食，與實驗中的「高脂飲食」原理類似，在攝入低碳水的前提下，攝入大量優質脂肪，讓身體進入脂肪代謝的燃脂模式，無關食慾多寡，都能吃成健康的瘦子。
[1] Asprosin is a centrally acting orexigenic hormone. Nature Medicine ( IF 29.886 ) 2017,11
https://www.researchgate.net/publication/320886250_Asprosin_is_a_centrally_acting_orexigenic_hormone
[2] Asprosin, a fasting-induced glucogenic protein hormone[J]. Cell, 2016, 165(3): 566-579.
https://www.sciencedirect.com/science/article/pii/S0092867416302136
[3] Ghrelin Enhances Appetite and Increases Food Intake in Humans. The Journal of Clinical Endocrinology and Metabolism,2001,86(10)
https://academic.microsoft.com/#/detail/2069302715
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