Obesity and adipokines are associated with a state of chronic low grade inflammation (Trayhurn & Wood 2004).In view of our findings that the adipokines resistin and fiaf (fasting-induced adipose factor) are also expressed in mouse brain and pituitary gland (Wiesner et al 2004), we tested the hypothesis that these factors would be induced in brain tissue following cerebral hypoxia/ischemia (H/I). Neonatal H/I (postnatal day 8; unilateral common carotid artery occlusion under isoflurane anaesthesia, plus exposure to 8% oxygen; 60 mins) increased fiaf expression (Real Time RT-PCR), but not resistin mRNA, in ipsilateral mouse cerebral cortex and hippocampus at 2 days (1.4 to 1.9-fold; P< 0.01) and 7 days (1.8-fold; P< 0.001) post-H/I. In contrast resistin mRNA was significantly increased (1.8-fold; P<0.001) in cortex only after 21 days, when fiaf mRNA levels had returned to baseline. Since fiaf is a PPARα target gene, we also tested the effects of the PPARα agonist WY-14643 (Tocris; 50 microgm per gm b.wt; s.c.; male mice; 28 days old). This drug acutely (3hr) increased fiaf (2.2-fold; P<0.01), but not resistin, expression in cerebral cortex, but induced down-regulation of fiaf mRNA (P<0.01) in cortex, pituitary and fat after 3 daily injections. Our data suggest that brain-derived adipokines, such as FIAF and resistin,are involved in cerebral inflammation following ischemic injury. Funded by NSHRF, CIHR and NHF (Australia).
01 - 05 Apr 2006
European Society of Endocrinology