Systemic Nanoparticle-Mediated Delivery of Pantetheinase Vanin-1 Regulates Lipolysis and Adiposity in Abdominal White Adipose Tissue
Systemic Nanoparticle-Mediated Delivery of Pantetheinase Vanin-1 Regulates Lipolysis and Adiposity in Abdominal White Adipose Tissue
复制标题
全身纳米颗粒介导的泛酸酶 Vanin-1 调节腹部白色脂肪组织中的脂肪分解和肥胖
DOI：
10.1002/advs.202000542
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发表时间：
2020-06-08
期刊：
影响因子：
15.1
通讯作者：
Liu, Chang
中科院分区：
文献类型：
--
作者：
Chen, Siyu;Zhang, Wenxiang;Liu, Chang
Lipolysis in white adipose tissue (WAT) occurs in response to nutritional signals and helps to regulate lipid turnover/adiposity in animals. However, the causal relationships and the mechanisms controlling WAT morphology are not clear. In this report, Vanin-1, a pantetheinase, is shown to be a novel determinant for lipolysis and adiposity. The expression of Vanin-1 in the abdominal WAT is positively correlated with lipolysis both in mice and in humans. Mice with global Vanin-1 deficiency exhibit adipocyte hypertrophy and impaired lipolysis. Use of a nanosystem comprising P3-peptide, chitosan oligosaccharide lactate, and polyethylene glycol that controls Vanin-1 expression in the abdominal WAT shows that WAT-specific Vanin-1 knockdown blocks fasting-induced lipolysis and prevents WAT loss. However, WAT-specific Vanin-1 mRNA restoration rescues impaired lipolysis and improves glucose/insulin intolerance in diabetic db/db mice. Mechanistically, Vanin-1 induces PPAR gamma activity and subsequently facilitates its activation on the proximal promoters of lipolytic genes. Thus, an essential role of Vanin-1 in the regulation of lipolysis and adiposity is revealed, and a functional RNA delivering strategy for specific intervention of Vanin-1 expression in WAT is shown. These findings provide a promising approach to treat metabolic diseases caused by dysregulation of Vanin-1 and lipolysis.
