脂肪生成
内分泌学
内科学
3T3-L1
化学
生物
脂肪组织
医学
作者
Yun Liu,Rihua Zhang,Xin Jing,Yan Sun,Jie Li,Dong Wei,Allan Z. Zhao
出处
期刊:Endocrinology
[The Endocrine Society]
日期:2011-03-01
卷期号:152 (3): 903-911
被引量:46
摘要
S100A16 is a member of S100 protein super family that carries calcium-binding EF-hand motifs. Its expression is ubiquitous and elevated in various types of tumors. The functions of S100 proteins are still being defined, although many members of S100 protein family are traditionally considered as markers of tumor tissues. Using 3T3-L1 preadipocyte model, we investigated the expression and function of S100A16 during differentiation into adipocytes as well as the potential roles of S100A16 in the regulation of insulin sensitivity. We found that the expression of S100A16 was increased during differentiation and that elevation of intracellular Ca2+ via calcium ionophores led to its nucleus exclusion. Overexpression of S100A16 in 3T3-L1 preadipocytes increased their proliferation and markedly enhanced adipogenesis but resulted in significant reduction of insulin-stimulated glucose uptake and phosphorylation of AKT. In contrast, suppression of S100A16 expression with two different types of RNA interference significantly inhibited adipogenesis and preadipocyte proliferation. Immunoprecipitation analysis revealed that S100A16 could physically interact with tumor suppressor protein p53, also a known inhibitor of adipogenesis. Overexpression or RNA interference–initiated reduction of S100A16 led to the inhibition or activation of the expression of p53-responsive genes, respectively. Interestingly, Western blot assays showed that S100A16 protein levels were markedly higher in the adipose tissues of diet-induced obese mice and the ob/ob mice than that in control lean mice. Thus, we reveal for the first time that S100A16 protein is a novel adipogenesis-promoting factor and that increased expression of S100A16 in 3T3-L1 adipocytes can have a negative impact on insulin sensitivity.
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