Endocrine Abstracts

Adipokines such as resistin and FIAF (fasting-induced adipose factor) are predominantly, but not exclusively, expressed in adipose tissue and may modulate insulin sensitivity and lipid metabolism. We reported that resistin and fiaf mRNA, and resistin protein, are detectable in the mouse hypothalamus and pituitary gland (see eg. Wiesner et al. 2004). We are investigating the regulation of these genes in a novel hypothalamic neuronal cell line (n-1; Belsham et al. 2004). Over-expressing the transcription factor CEBPα increased resistin mRNA (8-fold, P<0.01), but reduced fiaf by 45% (P<0.01) and SOCS-3, an inhibitor of leptin signalling, by 35% (P<0.01; Real time RT-PCR). Conversely, attenuating resistin gene expression using a resistin-specific small interfering RNA (siRNA) reduced resistin expression by 55% (100 nM; P<0.001), but increased fiaf and SOCS-3 by 30% (P<0.01) and 22% (P<0.01) respectively. In contrast, a fiaf-specific siRNA reduced fiaf expression by 57% (100 nM; P<0.001), but SOCS-3 and resistin mRNA remained unchanged. A fiaf-encoding plasmid significantly increased fiaf mRNA 230-fold (P<0.01) in n-1 cells, but once again no changes in resistin or SOCS-3 expression were detected. These data suggest that brain-derived resistin can attenuate fiaf and SOCS-3 expression, and may contribute to the regulation of hypothalamic energy homeostasis. Funded by NSHRF, IWK, UIMRF/Capital Health and CIHR.