高糖飲食降低卵巢生殖幹細胞的增生和胰島素抵抗無關

Abstract

幹細胞能維持組織的恆定。除了組織內在的信號外，飲食也會影響幹細胞的功能。高糖飲食通常會導致肥胖，而肥胖後來可能發展為2型糖尿病，這是一種組織無法對胰島素作出反應 （insulin resistance,胰島素抵抗）導致血糖增加的慢性代謝疾病。然而，目前尚不清楚高糖飲食是否會損害幹細胞功能。我利用被研究得很清楚的果蠅卵巢生殖幹細胞來探討高糖飲食是否會影響幹細胞。我發現在果蠅產生胰島素抗性之前，高糖飲食就降低了果蠅卵巢生殖幹細胞（GSCs）的增生。高糖飲食餵養一周會導致脂肪細胞累積油滴（肥胖症），改變胰島素基因的轉錄，同時導致卵巢縮小，降低產卵量和減少GSC分裂，但是並不會造成胰島素抗性的產生。相反的，餵食高糖後都會增加對胰島素敏感度 （insulin sensitivity）; 不論母果蠅有沒有交配，都會增加果蠅對胰島素的敏感度，這個結果顯示有沒有交配不會影響母果蠅對胰島素的反應。有趣的是高糖飲食餵食的GSCs 累積高量的活性氧基（reactive Oxygen species），這可能會降低通過JNK途徑的細胞週期進程。我們的結果顯示，在2型糖尿病發生之前，高糖飲食會阻礙GSC功能，這種現象可能適用於不同物種的其他幹細胞系統。

Stem cells maintain tissue homeostasis throughout the adult lifespan. In addition to tissue-intrinsic signals, diet also affects stem cell function. A high-sugar diet often induces obesity, which can later progress to type 2 diabetes, a chronic metabolic disorder that involves insulin resistance and high blood sugar. However, it is not clear if and how high-sugar diet impairs stem cell function. Here, I report that a high-sugar diet decreases proliferation in Drosophila ovarian germline stem cells (GSCs) before insulin resistance occurs. One week of high-sugar diet feeding induces oil droplet accumulation in fat body (obesity) and alters insulin transcripts, while decreasing ovary size, egg production and GSC division in the absence of insulin resistance. On contrary, flies fed with high-sugar diet display increased insulin sensitivity. This increased response to insulin is observed in female flies with or without mating, suggesting that mating does not affect flies in response to insulin. Instead of insulin signaling impairment, GSCs under high-sugar diet display high ROS levels, which may decrease cell cycle progression via the JNK pathway. Interestingly, taken together, our results show that GSC function is impeded by high sugar levels prior to the onset of type 2 diabetes, and this phenomenon may apply to other stem cell systems across different species.