title: Diet-induced obesity attenuates cytokine production following an immune challenge.
abstract: Obesity increases susceptibility for numerous diseases and neurological disorders including cardiovascular disease, metabolic syndrome, and dementia. One factor that may contribute to the increased risk for these conditions is the development of chronic inflammation. The current study evaluated whether diet-induced obesity (DIO) affects cognitive performance by increasing neuroinflammation and prolonging the behavioral and inflammatory response to an immune challenge. Adult male C57BL/6J mice were fed a high-fat (60% fat) or control diet (10% fat) for 2 or 5 months. After consuming their respective diets for two months, sickness associated behaviors were assessed 4 and 24h after a lipopolysaccharide (LPS) or saline injection. In a separate experiment, DIO and control mice were tested for spatial learning in the water maze and challenged with LPS one month later. Peripheral cytokine production was assessed in adipose and spleen samples and the neuroinflammatory response was assessed in hippocampal, cortical, and brain samples. DIO impaired acquisition of a spatial learning task relative to control mice. However, these deficits are unlikely to be related to inflammation as DIO showed no changes in basal cytokine levels within the periphery or brain. Further, in response to LPS DIO mice showed comparable or attenuated levels of the proinflammatory cytokines interleukin-1β and interleukin-6 relative to control mice. DIO also reduced hippocampal expression of brain-derived neurotrophic factor and the pre-synaptic marker synaptophysin. Presently, the data indicate that DIO suppresses aspects of the immune response and that cognitive deficits associated with DIO may be related to reduced neurotrophic support rather than inflammation.
authors.affiliation: University of North Carolina Wilmington, Department of Psychology, Wilmington, NC, USA. Electronic address: kbaumgarner@uscupstate.edu.
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Baumgarner
authors.affiliation: University of North Carolina Wilmington, Department of Psychology, Wilmington, NC, USA. Electronic address: ses8535@uncw.edu.
authors.forename: Sharay
authors.initials: S
authors.lastname: Setti
authors.affiliation: University of North Carolina Wilmington, Department of Psychology, Wilmington, NC, USA. Electronic address: diazc@uncw.edu.
authors.forename: Carolyn
authors.initials: C
authors.lastname: Diaz
authors.affiliation: University of North Carolina Wilmington, Department of Psychology, Wilmington, NC, USA. Electronic address: aml8440@uncw.edu.
authors.forename: Alyssa
authors.initials: A
authors.lastname: Littlefield
authors.affiliation: University of North Carolina Wilmington, Department of Psychology, Wilmington, NC, USA. Electronic address: aj3294@uncw.edu.
authors.forename: Amanda
authors.initials: A
authors.lastname: Jones
authors.affiliation: University of North Carolina Wilmington, Department of Psychology, Wilmington, NC, USA. Electronic address: kohmanr@uncw.edu.
authors.forename: Rachel A
authors.initials: RA
authors.lastname: Kohman
mesh_terms: D000818:Animals; D001835:Body Weight; D001921:Brain / Q000276:immunology / Q000503:physiopathology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002540:Cerebral Cortex / Q000276:immunology / Q000503:physiopathology; D016207:Cytokines / Q000378:metabolism*; D059305:Diet, High-Fat / Q000009:adverse effects*; D006624:Hippocampus / Q000276:immunology / Q000503:physiopathology; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000502:physiology; D009765:Obesity / Q000276:immunology* / Q000503:physiopathology; D065853:Spatial Learning / Q000502:physiology; D013154:Spleen / Q000276:immunology / Q000378:metabolism; D016708:Synaptophysin / Q000378:metabolism; D013647:Task Performance and Analysis; D013997:Time Factors
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D016207:Cytokines; C587672:IL1B protein, mouse; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016708:Synaptophysin; C569015:Syp protein, mouse; C577686:interleukin-6, mouse
keywords: BDNF; CD74; High-fat diet; LPS; Spatial learning; Synaptophysin