Postprandial activation of protein kinase C� regulates the expression of adipocytokines via the transcription factor AP-2β

Abstract

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.

Regulation of interleukin-6 secretion by the two-pore-domain potassium channel Trek-1 in alveolar epithelial cells

“…In contrast, PKC-deficient airway epithelial cells produced increased levels of IL-6 (59). Other PKC isoforms have been reported to regulate IL-6 release in tissues other than the lung (26,55). Our data suggest that decreased PKC activity may be associated with impaired IL-6 secretion from AECs, as indicated by our data showing inhibition of IL-6 release by the PKC inhibitor calphostin C (Fig.…”

Genome-wide association study of triglyceride response to a high-fat meal among participants of the NHLBI Genetics of Lipid Lowering Drugs and Diet Network (GOLDN)

“…Three, chromosome 2 SNP rs7588818, with suggestive association to AUC after baseline TG adjustment (Table S4), shows a predicted allele-specific binding of transcription factor TFAP2B. It has been demonstrated in murine adipocytes that postprandial activation of protein kinase Cµ (PRKD1) regulates the expression of adipocytokines CCL2 (MCP-1), IL6 and adiponectin (ADIPOQ) via TFAP2B [58]. Although we observed numerous instances from ENCODE epigenetic data where a SNP allele would destroy an observed liver methylated CpG or maps within hepatic cell histone acetylation or methylation peaks, we can only speculate on the relevance of such to the PPL condition.…”

Nonalcoholic steatohepatitis versus steatosis: Adipose tissue insulin resistance and dysfunctional response to fat ingestion predict liver injury and altered glucose and lipoprotein metabolism

“…We speculate that a strong genetic background may underlie both the severe adipose tissue resistance to insulin antilipolytic action, leading to very high circulating FFA levels, and in the maladaptive response to fat ingestion, leading to an altered adiponectin/resistin response. Among novel candidate genes conferring susceptibility to obesity and its complications, the transcription factor, activator protein 2 beta, has been recently shown to promote adipocyte hypertrophy and IR and to down‐regulate adiponectin expression postprandially, shifting adipokine expression toward a proinflammatory profile 35, 36. Another potential culprit is that the endoplasmic reticulum (ER) resident thiol protein, ERp44, a key mediator of ER stress, has been shown to regulate post‐translational modifications of adiponectin, reducing adipocyte content and secretion of this adipokine 37, 38…”