Abstract
The steadily increasing epidemic of obesity continues at alarming rates, is an important public health problem, and expression changes of S100A16 and 11 β-hydroxysteroid dehydrogenase type 1(11β-HSD1) is attributable to the adipocyte differentiation. In our previous study, we found that 11β-HSD1 protein expression increased in S100A16-overexpressed 3T3-L1 cell model. In order to further investigate the relationship between S100A16 and 11β-HSD1, and the molecular mechanisms of S100A16-induced adipogenesis, we constructed S100A16 transgenic and knockout mouse, and S100A16-overexpressed 3T3-L1 preadipocyte cell. Using S100A16 transgenic (S100A16Tg/+) mice fed with normal fat diet (NFD) and high fat diet (HFD) diet model, we evaluated the effect of S100A16 on adipogenesis, expression of 11β-HSD1, and RNA sequencing and quantification of gene expression. Using the 3T3-L1 cell model, we examined the effect of S100A16 and 11β-HSD1 on pre-adipocyte differentiation, and cell signaling events of 11β-HSD1 overexpression induced by S100A16. We found that when compared with C57BL/6 mice, overexpression of S100A16 under the condition of HFD increased lipid content in WAT and fat infiltration in hepatocytes, 11β-HSD1 protein expression increased along with S100A16. Elevated S100A16 and 11β-HSD1 expression promoted adipogenesis in 3T3-L1 cells. Overexpression of S100A16 inhibited the degradation of 11β-HSD1. We conclude that S100A16-induced adipogenesis is associated with up-regulation of 11β-HSD1.
Highlights
Obesity is an important metabolic disorder and serious public health problem worldwide that is closely associated with various dangerous disease risk factors, such as insulin resistance and Type 2 diabetes
We demonstrated that up-regulation of S100A16 expression in adipose tissue promoted 11β-HSD1 expression, while down-regulation suppressed 11β-HSD1 expression, suggesting S100A16 may be associated with pre-adipocyte differentiation, obesity, and insulin resistance
The transgene was expressed at high levels in all tissues, and expression was especially high in white adipose tissue (WAT) and liver
Summary
Obesity is an important metabolic disorder and serious public health problem worldwide that is closely associated with various dangerous disease risk factors, such as insulin resistance and Type 2 diabetes. Due to the wide-ranging health implications, the need to better understand the cellular and molecular basis of adipocyte differentiation in order to develop new and effective strategies for obesity prevention has become acute [1,2]. S100 proteins are small, acidic calcium-binding proteins of 10–12 kDa in size that contain two distinct EF-hand motifs. The S100-specific EF-hand is located at the N-terminus, followed by a classical Ca2+-binding EF-hand that operates as a Ca2+-activated switch that interacts with and modulates the activity of a large number of targets [6]. The S100 protein family is involved in the regulation of diverse cellular processes such as cell growth, differentiation, and cell cycle progression. The recently identified S100 protein family member S100A16 has been linked with obesity, Type 2 diabetes, inflammation, and License 4.0 (CC BY)
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