Consumption of high fat diets (HFD) is associated with a short and long term inflammation of the hypothalamus¹, the brain’s glucose sensor and main regulator of energy balance in the brain². Notably, magnetic resonance spectroscopy (MRS) can provide in vivo reliable biomarkers of physiologic or pathologic conditions of the brain in a noninvasive manner³. On these grounds, the quantification of the in vivo changes in metabolites and neurotransmitters during HFD consumption using MRS could represent a powerful strategy with which to investigate the putative HFD induced inflammatory processes. The aim of this study was to evaluate HFD-induced modifications in the mouse hypothalamus in vivo by ¹H MRS. C57BL/6 mice (11weeks, n=12, 27±2g) were fed with a 10% kcal fat diet (http://www.researchdiets.com) during one week (baseline) and were then either switched to a 60% kcal fat (http://www.researchdiets.com) (n=6) or remained with the control diet (n=6). Body weight, glycaemia values and in vivo measurements of the neurochemical profile of the mouse hypothalamus were monitored at different time points (summarized in Figure 1). All MRS measurements were performed in a horizontal 14.1T/26cm magnet under 1-1.5% isofluorane anesthesia. A home-built quadrature surface coil with two geometrically decoupled single-turn loops (12 mm resonating at 600-MHz) was optimized to improve the sensitivity detection in the hypothalamus (1.8x2.7x1.8mm³). Field homogeneity was achieved with FAST(EST)MAP⁴, and localized 1H MR spectrum were obtained using SPECIAL⁵ (TE/TR = 2.8/4,000ms, Av=400). Water spectra (Av=8) were acquired for quantification of metabolites with LCModel. Two-way ANOVA tests followed by the post-test Bonferroni corrections were applied between the values of metabolites in the different time points.Figure 2 depicts a representative ¹H spectrum of the mouse hypothalamus in the baseline measurements –before switching diets-. SNR of the edited spectra was >20 for all cases, as measured from LCModel, and linewidths of total creatine at 3.0ppm <20Hz.. Within 7 days of high fat feeding, animals started increasing significantly their body weight, but control animals only showed significant increases within 6 months of monitoring, as shown in Figure 3 (two tailed paired t tests). Fasting glucose levels started to be significantly different between groups 1 month after changing the diet. Figure 4 illustrates the effects of the HFD (top) and control (bottom) animals in the neurochemical profile of the mouse hypothalamus during the 6 months. During the first 14 days, only controls show a significant increase in glucose (Glc) concentration, and HFD fed animals show no significant changes. From two months, Ins, Glc, the sum of glutamate and glutamine (Glu+Gln) and NAA increase significantly for the obese animals, and from 4 months taurine (Tau) and total creatine (Cr+PCr) also increase in a significant manner. In the long term period, the sole change in control animals is a significant decrease in ascorbate (Asc).Our findings indicate that high fat diet animals express modifications in the neurochemical profile of hypothalamus after two months of HFD feeding. Findings are in are in agreement with ongoing osmotic changes and inflammatory processes, as reported in diabetic animals⁷ and in in vitro studies of obesity development⁸. No relevant short-term changes were detected in our MRS study.