大江 发表于 2020-3-3 00:04:53

MPL脂肪营养不良综合征(Marfanoid-progeroid-lipodystrophy syndrome,MPL)

Marfanoid-progeroid-脂肪营养不良综合征(MPL),也称为Marfan lipodystrophy syndrome(MFLS)或progeroid fibrillinopathy,是一种极为罕见的医学疾病,表现为多种症状,包括通常与Marfan综合征相关的症状,其外观类似于新生儿早衰综合症(NPS;也称为Wiedemann–Rautenstrauch综合征)和严重的部分脂肪营养不良。这是一种遗传病,是由FBN1基因的突变引起的,该基因编码原纤维蛋白,并影响原纤维蛋白,纤维结构蛋白原纤维蛋白1和糖原蛋白激素白脂素的裂解产物。截至2016年,已报告的病例不到10例。 LizzieVelásquez和Abby Solomon因患有该病而在媒体上广为人知。

除了严重的脂肪营养不良(脂肪组织丢失)外,患有MPL的人还伴有明显的瘦组织质量损失,这也有助于他们的“瘦”外观。基于视觉检查,最初认为与MPL相关的脂肪营养不良。然而,实际上它似乎是局部的,局限于面部,远端,臀部的椎旁和外侧区域。在胸部和腹部的躯干中发现正常量的皮下脂肪。因此,患有MPL的女性的乳房是正常的。

患有MPL的人看起来早衰,但这不是由于实际的早期衰老,而是由于他们缺乏皮下脂肪。因此,MPL并不是真正的早衰形式。

2016年,发现与MPL相关的部分脂肪营养不良是由原纤维蛋白和新型糖原性蛋白激素C端结构域切割产物的损失引起的,这种激素被称为白脂素。由于proprosin缺乏症,MPL患者进食减少,体重增加或没有出现胰岛素抵抗等糖尿病症状。 MPL患者比正常人消耗更少的能量,但消耗的能量也更少,并且他们的净能量平衡被适度降低。与血液中无法检测到proprosin的MPL患者相反,肥胖和糖尿病患者的白脂素水平升高。这样,FBN1被昵称为“瘦基因”,针对肥胖抑制素信号的靶向抑制的药物开发被认为是治疗肥胖症和糖尿病的“异常有望的”潜在治疗途径。

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