title: Mark4 promotes adipogenesis and triggers apoptosis in 3T3-L1 adipocytes by activating JNK1 and inhibiting p38MAPK pathways.
abstract: BACKGROUND
  Microtubule affinity-regulating kinase 4 (MARK4) deficiency has been reported to negatively regulate diet-induced obesity and to mitigate insulin resistance in knockout mice, and thus may play a role in metabolic syndrome. However, the details of the molecular mechanism have yet to be revealed and the impacts of MARK4 on apoptosis remain unexplored. This study investigated the role of Mark4 in the regulation of lipid accumulation and apoptosis in adipocytes and analysed signalling pathways involved.
  
  
  RESULTS
  We found that Mark4 significantly up-regulated the expression of gene sterol regulatory element binding protein-1c (SREBP-1c), fatty acid synthase (FAS), acetyl-CoA carboxylase-α (ACCα) and peroxisome proliferator activated receptor-γ (PPARγ); and reduced the protein contents of adipose triglyceride lipase (ATGL), as evidenced by the dramatic increasing lipid droplet accumulation in 3T3-L1 cells. Furthermore, a terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) apoptosis assay showed that Mark4 triggered apoptosis of adipocytes; and apoptosis was confirmed by the decreased protein contents of B-cell lymphoma-2 (Bcl-2), full-length caspase-3 and full-length caspase-9, as well as the increased expression of Bax, cleaved caspase-3 and cleaved caspase-9. Analysis of special inhibitors allowed us to offer the following explanation for these impacts of Mark4: activation of Jun N-terminal kinase1 (JNK1) promoted both apoptosis and adipogenesis, whereas inhibition of the p38 mitogen-activated protein kinase (p38MAPK) pathway contributed to lipid accumulation alone.
  
  
  CONCLUSIONS
  Mark4 promotes adipogenesis in 3T3-L1 adipocytes by activating the JNK1 and inhibiting the p38MAPK pathway, and triggers apoptosis by activating the JNK1 pathway. We conclude that anti-Mark4 therapy targetted to inhibit lipid accumulation and apoptosis of adipocytes shows potential as a novel therapeutic strategy for treatment of obesity-associated metabolic complications.
authors.affiliation: College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, China.
authors.forename: Min
authors.initials: M
authors.lastname: Feng
authors.forename: Liang
authors.initials: L
authors.lastname: Tian
authors.forename: Lu
authors.initials: L
authors.lastname: Gan
authors.forename: Zhenjiang
authors.initials: Z
authors.lastname: Liu
authors.forename: Chao
authors.initials: C
authors.lastname: Sun
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000502:physiology; D050156:Adipogenesis; D000818:Animals; D017209:Apoptosis; D004789:Enzyme Activation; D051379:Mice; D048055:Mitogen-Activated Protein Kinase 8 / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: C482979:MARK4 protein, mouse; D017346:Protein Serine-Threonine Kinases; D048055:Mitogen-Activated Protein Kinase 8; D048051:p38 Mitogen-Activated Protein Kinases
keywords: JNK1pathway; Mark4; adipogenesis; apoptosis; p38MAPK pathway