FAM3A enhances adipogenesis of 3T3-L1 preadipocytes via activation of ATP-P2 receptor-Akt signaling pathway.

Yujing Chi,Zhenzhen Chen,Na Li,Jing Li,Liping Ma,Weikang Peng,Xiuying Pan,Qinghua Cui,Yulan Liu,Weidong Yu,Bin Geng,Mei Li,Xiangjun He,Jichun Yang

doi:10.18632/oncotarget.17578

Yujing Chi, Zhenzhen Chen + Show 12 more

Open Access

https://doi.org/10.18632/oncotarget.17578

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Abstract

FAM3A plays important roles in regulating hepatic glucose/lipid metabolism and the proliferation of VSMCs. This study determined the role and mechanism of FAM3A in the adipogenesis of 3T3-L1 preadipocytes. During the adipogenesis of 3T3-L1 preadipocytes, FAM3A expression was significantly increased. FAM3A overexpression enhanced 3T3-L1 preadipocyte adipogenesis with increased phosphorylated Akt (pAkt) level, whereas FAM3A silencing inhibited 3T3-L1 preadipocyte adipogenesis with reduced pAkt level. Moreover, FAM3A silencing reduced the expression and secretion of adipokines in 3T3-L1 cells. FAM3A protein is mainly located in mitochondrial fraction of 3T3-L1 cells and mouse adipose tissue. FAM3A overexpression increased, whereas FAM3A silencing decreased ATP production in 3T3-L1 preadipocytes. FAM3A-induced adipogenesis of 3T3-L1 preadipocytes was blunted by inhibitor of P2 receptor. In white adipose tissues of db/db and HFD-fed obese mice, FAM3A expression was reduced. One-month rosiglitazone administration upregulated FAM3A expression, and increased cellular ATP content and pAkt level in white adipose tissues of normal and obese mice. In conclusion, FAM3A enhances the adipogenesis of preadipocytes by activating ATP-P2 receptor-Akt pathway. Under obese condition, a decrease in FAM3A expression in adipose tissues plays important roles in the development of adipose dysfunction and type 2 diabetes.

Highlights

Obesity, a clinical condition characterized by the excessive accumulation of body fat, is a strong risk factor for type 2 diabetes [1, 2]
Rosiglitazone administration upregulated family with sequence similarity 3 member A (FAM3A) expression in high fat diet (HFD)-fed diabetic mouse tissues with improved adipokine profile and hyperglycemia. These findings suggested that a decrease in FAM3A expression in adipose tissues contributes to the development of adipose dysfunction and type 2 diabetes
To initially determine whether FAM3A is involved in adipogenic process, C57BL/6 mice were orally administrated with rosiglitazone for one month, and FAM3A expression in white adipose tissue was determined

Summary

Introduction

A clinical condition characterized by the excessive accumulation of body fat, is a strong risk factor for type 2 diabetes [1, 2]. Specific deletion of PPARγ in adipose causes lipodystrophy, global insulin resistance and www.impactjournals.com/oncotarget hyperglycemia in mice [7]. This paradox of obesity and type 2 diabetes suggested that more studies are still needed to explore the role of adipose tissues in the development of type 2 diabetes under obese condition. Under the condition of excessive nutrients, an impairment in the capacity of preadipocyte adipogenesis will cause adipose dysfunction, leading to ectopic lipid deposition and disturbed adipokine expression/secretion [8, 18]

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Conclusion