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

Oncotarget. 2017 Jul 11;8(28):45862-45873. doi: 10.18632/oncotarget.17578.

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.

Keywords: ATP; FAM3A; P2 receptor; PPARγ; adipogenesis.

MeSH terms

  • 3T3-L1 Cells
  • Adenosine Triphosphate / metabolism*
  • Adipocytes / cytology*
  • Adipocytes / metabolism*
  • Adipogenesis*
  • Adipose Tissue, White / cytology
  • Adipose Tissue, White / metabolism
  • Animals
  • Cell Differentiation / genetics
  • Cytokines / genetics*
  • Gene Expression Regulation / drug effects
  • Gene Silencing
  • Male
  • Mice
  • PPAR gamma / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Receptors, Purinergic P2 / metabolism*
  • Rosiglitazone
  • Signal Transduction*
  • Thiazolidinediones / pharmacology

Substances

  • Cytokines
  • FAM3A protein, mouse
  • PPAR gamma
  • Receptors, Purinergic P2
  • Thiazolidinediones
  • Rosiglitazone
  • Adenosine Triphosphate
  • Proto-Oncogene Proteins c-akt