Poster Session 2 - E4
1Andy Tran, 1Neruja Loganathan, 1Emma Mcilwraith, 1,2,3Denise D. Belsham
1 Physiology; 2 Obstetrics and Gynaecology; 3 Medicine, University of Toronto, Toronto, ON, Canada
Spexin (SPX) is a recently discovered peptide that binds to galanin receptors 2 (GalR2) and 3 (GalR3) to exert its functions. Emerging evidence implicates SPX as a modulator of satiety and energy balance as circulating SPX levels appear to be dysregulated in obesity. It is currently unknown how SPX and its receptors are regulated in the hypothalamus, an area critical for energy homeostasis. We therefore examined hypothalamic SPX, GalR2 and GalR3 gene expression in response to several compounds in a clonal adult-derived hypothalamic cell model, mHypoA-59, using quantitative reverse transcription PCR (qRT-PCR). We hypothesized that SPX and its receptors would be regulated by bisphenol A (BPA), an endocrine disrupting chemical and obesogen; palmitate, a dietary saturated fatty acid; and at least one of PKA, PKC or PKG which are protein kinases involved in different intracellular signalling pathways. SPX and GalR3 mRNA was maximally upregulated at 8 hours when treated with: 50 uM of palmitate, 100 uM of bisphenol A and 100 uM of sodium nitroprusside (SNP), a nitric oxide donor that can stimulate cGMP formation and subsequently activate the PKG pathway. GalR2 mRNA was maximally upregulated at 8 hours when treated with 50 uM of palmitate and 100 uM of SNP. Conversely, 100 uM of BPA downregulated GalR2 mRNA at 16 and 24 hours. These results suggest regulatory roles for BPA, palmitate, and nitric oxide in SPX, GalR2 and GalR3 gene expression. Elucidating the pathways that regulate gene expression of SPX and its receptors in the hypothalamus will contribute to current models of central energy balance and provide insight into how components of this regulatory circuit may be dysregulated in obesity.