High fat diet alters the inflammatory response in the hippocampus and the hypothalamus of non-obese male mice with regional specificity

ASTIZ, MARIANA; PERNÍA, OLGA; BARRIOS, VICENTE; GARCIA-SEGURA, LUIS M; DIZ-CHAVES, YOLANDA

Milano

Congreso; FENS (Federation of European Neuroscience Societies) Forum Neuroscience; 2014

FENS (Federation of European Neuroscience Societies)

Before obesity develops, high fat diet (HFD) may induce metabolic/inflammatory adaptations with different outcomes within the brain. We aimed to compare the response to an acute (24h) inflammatory insult (LPS i.p. 5 mg/Kg bw) in the hippocampus and the hypothalamus of adult male mice after 15 days of HFD. We measured the expression of inflammatory mediators (TNFα, IL6, IP10, mPGEs and IL10), molecules linking inflammatory/metabolic effects (SOCS3, STAT3, NFκB pathway members, TLR4), glial markers (GFAP, Vimentin, Emr1 and CD68) and mitochondrial metabolic and morphology markers (UCP2 and Mfn 1). HFD did not significantly affect the LPS-induced changes in the expression of these molecules in the hippocampus compared to animals receiving low fat diet (LFD). In contrast, HFD decreased the LPS-induced changes in the hypothalamus. The differential response to HFD could be attributed in part to the different regulation of the expression of glucocorticoid receptor (GR). LPS increased corticosterone circulating levels and reduced the expression of GR in both structures in LFD animals. HFD did not affect GR expression in the hippocampus but decreased corticotropin releasing hormone (CRH) and GR expression in the hypothalamus under basal conditions. In addition LPS increased CRH and GR expression in the hypothalamus of HFD animals. These findings suggest that the hippocampus is relatively preserved for the effects of HFD. In contrast, HFD induces an impaired acute inflammatory response in the hypothalamus that could be due to an altered response to hypothalamus-pituitary-adrenal axis activity.