The response of the hypothalamus to leptin and a high-fat diet in mice

Energy homeostasis is regulated by the hypothalamus but fails when animals are fed a high-fat diet (HFD), and leptin insensitivity and obesity develops. We have used a microarray-based transcriptomics approach to identify novel genes regulated by HFD and leptin in the hypothalamus using mouse global arrays. For the transcriptomics studies male, 16 week old, C57BL/6J mice were obtained from Charles River laboratories (Maastricht, the Netherlands) and housed in pairs in the light and temperature-controlled animal facility of Wageningen University (12:12 h light/dark cycle at 22⁰C). Mice were maintained for 1 or 4 weeks on either a HFD (45% kCal from fat) or LFD (10% kCal from fat) (D12451 and D12450B respectively Research Diets, NJ, US). Please see http://www.researchdiets.com/opensource-diets/stock-diets/dio-series-diets for diet composition details. The fat source in this experiment was palm oil. Mice were then challenged with three intraperitoneal (IP) injections of recombinant mouse leptin (2 mg/kg body weight) (R&D Systems, Abingdon, UK) or vehicle at 24, 15 and approximately 3 hours prior to killing in the early morning (n=10). This experiment was part of the NuGO Proof of Principle studies