Experimental and Translational Research Center, Beijing Friendship Hospital, Capital Medical University , Beijing , China.
Institute of Cardiovascular Sciences and Key Laboratory of Molecular Cardiovascular Sciences, School of Basic Medical Sciences, Ministry of Education, Peking University Health Science Center , Beijing , China.
Am J Physiol Endocrinol Metab. 2019 Jan 1;316(1):E54-E62. doi: 10.1152/ajpendo.00180.2018. Epub 2018 Nov 20.
Seipin deficiency is responsible for type 2 congenital generalized lipodystrophy with severe loss of adipose tissue and can lead to hepatic steatosis, insulin resistance (IR), and dyslipidemia in humans. Adipose tissue secretes many adipokines that are central to the regulation of metabolism. In this study, we investigated whether transplantation of normal adipose tissue could ameliorate severe hepatic steatosis, IR, and dyslipidemia in lipoatrophic seipin knockout (SKO) mice. Normal adipose tissue from wild-type mice was transplanted into 6-wk-old SKO mice. At 4 mo after adipose tissue transplantation (AT), the transplanted fat survived with detectable blood vessels, and the reduced levels of plasma leptin, a major adipokine, were dramatically increased. Severe hepatic steatosis, IR, and dyslipidemia in SKO mice were ameliorated after AT. In addition, abnormal hepatic lipogenesis and β-oxidation gene expression in SKO mice were improved after AT. Our results suggest that AT may be an effective treatment to improve lipodystrophy-associated metabolic disorders.
Seipin 缺乏导致 2 型先天性全身性脂肪营养不良，严重丧失脂肪组织，可导致人类肝脂肪变性、胰岛素抵抗 (IR) 和血脂异常。脂肪组织分泌许多脂肪因子，这些因子对代谢调节至关重要。在这项研究中，我们研究了正常脂肪组织移植是否可以改善脂肪营养不良性 seipin 敲除 (SKO) 小鼠的严重肝脂肪变性、IR 和血脂异常。将野生型小鼠的正常脂肪组织移植到 6 周龄 SKO 小鼠体内。脂肪组织移植 (AT) 后 4 个月，移植的脂肪存活并检测到血管，主要脂肪因子血浆瘦素水平显著降低。AT 后可改善 SKO 小鼠的严重肝脂肪变性、IR 和血脂异常。此外，AT 后改善了 SKO 小鼠异常的肝脂肪生成和β氧化基因表达。我们的结果表明，AT 可能是改善脂肪营养不良相关代谢紊乱的有效治疗方法。
