Palmitic Acid Modulation of the Insulin-Like Growth Factor System in Hypothalamic Astrocytes and Neurons

Abstract

<b><i>Introduction:</i></b> Insulin-like growth factor (IGF)1 and IGF2 have neuroprotective effects, but less is known regarding how other members of the IGF system, including IGF binding proteins (IGFBPs) and the regulatory proteinase pappalysin-1 (PAPP-A) and its endogenous inhibitor stanniocalcin-2 (STC2) participate in this process. Here, we analyzed whether these members of the IGF system are modified in neurons and astrocytes in response to palmitic acid (PA), a fatty acid that induces cell stress when increased centrally. <b><i>Methods:</i></b> Primary hypothalamic astrocyte cultures from male and female PND2 rats and the pro-opiomelanocortin (POMC) neuronal cell line, mHypoA-POMC/GFP-2, were treated with PA, IGF1 or both. To analyze the role of STC2 in astrocytes, siRNA assays were employed. <b><i>Results:</i></b> In astrocytes of both sexes, PA rapidly increased cell stress factors followed by increased <i>Pappa</i> and <i>Stc2</i> mRNA levels and then a decrease in <i>Igf1</i>, <i>Igf2</i>, and <i>Igfbp2</i> expression and cell number. Exogenous IGF1 did not revert these effects. In mHypoA-POMC/GFP-2 neurons, PA reduced cell number and <i>Pomc</i> and <i>Igf1</i> mRNA levels, and increased <i>Igfbp2</i> and <i>Stc2</i>, again with no effect of exogenous IGF1. PA increased STC2 expression, but no effects of decreasing its levels by interference assays or exogenous STC2 treatment in astrocytes were found. <b><i>Conclusions:</i></b> The response of the IGF system to PA was cell and sex specific, but no protective effects of the IGFs were found. However, the modifications in hypothalamic PAPP-A and STC2 indicate that further studies are required to determine their role in the response to fatty acids and possibly in metabolic control.