Abstract # 1851 Gene expression profile of the interferon pathway in the brains of diet-induced obese mice

Abstract

Diet-induced obesity (DIO) has a known capacity to perturb CNS tissue homeostasis through its promotion of low-grade, systemic inflammation. Inflammation has routinely been identified as an underlying pathological component in numerous neurological diseases. While multiple signaling pathways converge to produce the highly orchestrated inflammatory response, the role of the interferon pathway within the brain following DIO remains relatively unknown. In an effort to shed potentially novel insight into the transcriptional activity of Type I interferon signaling pathway in the brains of DIO mice, we have characterized relative gene expression patterns using quantitative RT-PCR. Microdissections were performed on the striatum (STR), cerebral cortex (CTX), substantia nigra (SN), and hippocampus (HP) of male C57BL/6 mice following 12 weeks of a high-fat diet (60% kcal from fat) and qRT-PCR completed with RT2 profiler arrays (Qiagen). Key results have indicated that the greatest trends of interferon-related activity were observed across the SN, CTX, and STR, with the up-regulation of interferon-inducible genes (IFI30, IFIT3, IFITM1, and IFITM2). The CTX alone demonstrated up-regulated of interferon alpha genes (IFNA4, IFNAR1, and IFNAR2), while JAK/STAT genes were preferentially up-regulated in the SN. These findings link our observations of Type I interferon pathway activation in the brain with inflammation routinely observed by others following DIO, and may provide vital mechanistic insight that could ultimately aid the development of therapeutics directed at mitigating neuroinflammation.