Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an endoplasmic reticulum-resident protein and a secretory factor and has beneficial effects in multiple diseases. Recent evidence shows that its circulating levels in humans are dynamically regulated under various metabolic diseases, including diabetes, obesity, fatty liver, and cardiovascular diseases, suggesting that MANF may play a role in these pathological states. Also, its downregulation in mice impairs glucose homeostasis, promotes lipid accumulation in the liver, reduces energy expenditure, and induces inflammation. Conversely, MANF overexpression prevents or mitigates some of these metabolic disturbances. In particular, systemic MANF administration alleviates dietary obesity and related metabolic disorders in obese mice. We therefore propose that MANF might be a promising target for treating chronic metabolic diseases.

中脑星形胶质细胞源性神经营养因子 (MANF) 是一种内质网驻留蛋白和分泌因子，在多种疾病中具有有益作用。最近的证据表明，其在人体中的循环水平在各种代谢疾病下受到动态调节，包括糖尿病、肥胖、脂肪肝和心血管疾病，这表明 MANF 可能在这些病理状态中发挥作用。此外，它在小鼠中的下调会损害葡萄糖稳态，促进肝脏中的脂质积累，减少能量消耗并诱发炎症。相反，MANF 过表达可防止或减轻其中一些代谢紊乱。特别是，全身性 MANF 给药可减轻肥胖小鼠的饮食肥胖和相关代谢紊乱。