title: Short-Term High-Fat Diet Feeding Provides Hypothalamic but Not Hippocampal Protection against Acute Infection in Male Mice.
abstract: Obesity is associated with increased fever and sickness behavior in response to infection. The hypothalamic-pituitary-adrenal (HPA) axis plays a key role in the reaction to immune stimuli. Bacterial infection, or bacterial lipopolysaccharide (LPS), induces the expression of peripheral cytokines that stimulate the hypothalamus and the hippocampus and activate the HPA axis. In this study, we explored whether the hypothalamic and hippocampal responses to infection are altered during the development of diet-induced obesity. Male mice were exposed to a high-fat diet (HFD) or a low-fat diet (LFD) for 15 days. They were then administered a single intraperitoneal injection of bacterial LPS or vehicle and sacrificed 24 h later. LPS increased circulating levels of insulin and leptin, but only in LFD animals. LPS induced a significant decrease in hypothalamic corticotrophin-releasing hormone and glucocorticoid receptor mRNA levels in LFD animals but exerted the opposite effect in HFD-fed mice. LPS increased the hypothalamic expression of molecules involved in the leptin signaling pathway (SOCS3 and STAT3), nuclear factor-κB pathway members, inflammatory mediators (tumor necrosis factor-α and interleukin-6) and glial proliferation markers (Emr1 and CD68) in LFD animals. These effects were dampened in HFD-fed mice. In contrast, the hippocampal responses to LPS were largely insensitive to HFD. These results suggest that HFD feeding reduced the inflammatory response induced by LPS in the hypothalamus but not in the hippocampus.
authors: Instituto Cajal, CSIC, Madrid, Spain.
authors: Mariana
authors: M
authors: Astiz
authors: Olga
authors: O
authors: Pernía
authors: Vicente
authors: V
authors: Barrios
authors: Luis Miguel
authors: LM
authors: Garcia-Segura
authors: Yolanda
authors: Y
authors: Diz-Chaves
mesh_terms: D052242:Adiponectin / Q000097:blood; D000704:Analysis of Variance; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003346:Corticotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects*; D004041:Dietary Fats; D004195:Disease Models, Animal; D004435:Eating / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000097:blood / Q000209:etiology*; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D052242:Adiponectin; D016207:Cytokines; D004041:Dietary Fats; D007328:Insulin; D020738:Leptin; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; D003346:Corticotropin-Releasing Hormone