Resume |
We have recently reported that PPARa deficiency
leads to hypoglycaemia and hypoinsulinemia in
mice (Yessoufou et al. Endocrinology 147:4410–4418,
2006). Besides, these mice exhibited high adiposity with an
inflammatory state. We, therefore, assessed, in this study,
the effects of PPARα deficiency on the expression of
mRNA encoding for the insulin gene transcription factors
in pancreatic b-cells along with those implicated in
inflammation in adipose tissues. On fasting, the adult
PPARα-null mice were hypoglycemic. Serum insulin concentrations
and its pancreatic mRNA transcripts were
downregulated in PPARα-null mice, suggesting that
PPARα gene deletion contributes to low insulin gene
transcription. The PPARα gene deletion downregulates the
mRNA expression of insulin gene transcription factors, i.e.,
Pdx-1, Nkx6.1, and MafA. Besides, the pancreatic function
was diminished by PPARα deficiency as PPARα -null mice
expressed low pancreatic Glut2 and glucokinase mRNA.
PPARα-null mice also expressed high adiponectin and leptin mRNA levels compared to wild type animals. Adipose
tissues of PPARα-null mice exhibited upregulation of
CD14 and CD68 mRNA, generally expressed by macrophages.
PPARα gene deletion downregulates the adipocyte
mRNA of certain pro-inflammatory agents, like MCP-1,
TNF-a, IL-1b, IL-6, and RANTES, though pro-inflammatory
TLR-2 and TLR-4 mRNAs were upregulated in the
adipose tissues. Our results suggest that PPARα deficiency,
in mice, is implicated in the modulation of insulin gene transcription and in-flammatory status in adipose tissues. |