Obesity-induced neuroinflammation and cognitive impairment in young adult versus middle-aged mice

Immunity & Ageing

Research

Junguk Hur¹  Kai Guo¹  John Hayes²  Eva L. Feldman²  Adam A. Allouch²  Sarah E. Elzinga²  Faye E. Mendelson²  Rosemary E. Henn²  Ian Webber-Davis²  Emily Glass³  Rachel Parent³  Geoffery G. Murphy³ 

[1] Department of Biomedical Sciences, University of North Dakota, 58202, Grand Forks, ND, USA;Department of Neurology, University of Michigan, 48109, Ann Arbor, MI, USA;NeuroNetwork for Emerging Therapies, University of Michigan, 48109, Ann Arbor, MI, USA;Michigan Neuroscience Institute, University of Michigan, 48109, Ann Arbor, MI, USA;Department of Molecular and Integrative Physiology, Division of Cardiovascular Medicine, University of Michigan, 48109, Ann Arbor, MI, USA;

关键词: Aging;    Cognitive impairment;    High-fat diet;    Obesity;    Mouse;    Inflammation;    Brain;    RNA-seq;   

DOI  :  10.1186/s12979-022-00323-7

 received in 2022-08-26, accepted in 2022-12-05,  发布年份 2022

来源: Springer

【 摘 要 】

BackgroundObesity rates are increasing worldwide. Obesity leads to many complications, including predisposing individuals to the development of cognitive impairment as they age. Immune dysregulation, including inflammaging (e.g., increased circulating cytokines) and immunosenescence (declining immune system function), commonly occur in obesity and aging and may impact cognitive impairment. As such, immune system changes across the lifespan may impact the effects of obesity on neuroinflammation and associated cognitive impairment. However, the role of age in obesity-induced neuroinflammation and cognitive impairment is unclear. To further define this putative relationship, the current study examined metabolic and inflammatory profiles, along with cognitive changes using a high-fat diet (HFD) mouse model of obesity.ResultsFirst, HFD promoted age-related changes in hippocampal gene expression. Given this early HFD-induced aging phenotype, we fed HFD to young adult and middle-aged mice to determine the effect of age on inflammatory responses, metabolic profile, and cognitive function. As anticipated, HFD caused a dysmetabolic phenotype in both age groups. However, older age exacerbated HFD cognitive and neuroinflammatory changes, with a bi-directional regulation of hippocampal inflammatory gene expression.ConclusionsCollectively, these data indicate that HFD promotes an early aging phenotype in the brain, which is suggestive of inflammaging and immunosenescence. Furthermore, age significantly compounded the impact of HFD on cognitive outcomes and on the regulation of neuroinflammatory programs in the brain.

【 授权许可】

CC BY   
© The Author(s) 2022

【 图 表 】

Fig. 2

Fig. 1

41408_2022_764_Article_IEq30.gif

41408_2022_764_Article_IEq15.gif

Fig. 2