title: Postprandial activation of protein kinase Cµ regulates the expression of adipocytokines via the transcription factor AP-2β.
abstract: Abnormal secretion of adipocytokines promotes atherosclerosis, diabetes and insulin resistance, and is mainly induced by adipocyte hypertrophy. Recently, the circulating adipocytokine concentrations were reported to change in the postprandial period, as the levels of TNFα, IL-6 IL-8 and MCP-1 increased after a meal, whereas that of adiponectin decreased. These data suggest that prandial modulation of cytokines may be involved in the pathogenesis of atherosclerosis in type 2 diabetes. However, the regulatory mechanism of such change is still unclear. In the present study, we identified this mechanism with a special focus on the functions of protein kinase C (PKC) and of the transcription factor AP-2β, both of which are associated with the pathophysiology of adipocytokine regulation. PKCµ was highly phosphorylated in the re-feeding condition compared to the fasting condition in mouse adipose tissue, while other PKC isoforms remained unchanged. Furthermore, overexpression of PKCµ in 3T3-L1 adipocytes, but not other PKC isoforms, positively regulated the mRNA expression and promoter activity of MCP-1 and IL-6, and negatively regulated those of adiponectin. AP-2β had similar effects on the expression and promoter activity of these adipocytokines. Interestingly, overexpression of PKCµ enhanced the stimulatory and inhibitory effects of AP-2β on the expression of these adipocytokines. Finally, PKCµ could not activate a mutant MCP-1 promoter lacking the AP-2β binding domain. Our results suggest that postprandial activation of PKCµ plays a role in disordered postprandial adipocytokine expression through AP-2β.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, Shiga University of Medical Science, Seta, Tsukinowa-cho, Otsu, Shiga 520-2192, Japan. dorch@belle.shiga-med.ac.jp
authors.forename: Motoyuki
authors.initials: M
authors.lastname: Kondo
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ugi
authors.forename: Katsutaro
authors.initials: K
authors.lastname: Morino
authors.forename: Tomoya
authors.initials: T
authors.lastname: Fuke
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Obata
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yoshizaki
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Nishio
authors.forename: Shiro
authors.initials: S
authors.lastname: Maeda
authors.forename: Atsunori
authors.initials: A
authors.lastname: Kashiwagi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Maegawa
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism; D054392:Adipokines / Q000235:genetics / Q000378:metabolism*; D052242:Adiponectin / Q000235:genetics / Q000378:metabolism; D000818:Animals; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019518:Postprandial Period; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D050656:Transcription Factor AP-2 / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation
chemical_list: D054392:Adipokines; D052242:Adiponectin; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D015850:Interleukin-6; D050656:Transcription Factor AP-2; C089212:protein kinase D; D011493:Protein Kinase C