TitleAmelioration of Metabolic Syndrome-Associated Cognitive Impairments in Mice via a Reduction in Dietary Fat Content or Infusion of Non-Diabetic Plasma.
Publication TypeJournal Article
Year of Publication2016
AuthorsJohnson LA, Zuloaga KL, Kugelman TL, Mader KS, Morré JT, Zuloaga DG, Weber S, Marzulla T, Mulford A, Button D, Lindner JR, Alkayed NJ, Stevens JF, Raber J
Date Published2016 Jan
KeywordsAnimals, Behavior, Animal, Cerebrovascular Circulation, Cluster Analysis, Cognition Disorders, Diet, High-Fat, Dietary Fats, Disease Models, Animal, Female, Maze Learning, Metabolic Syndrome, Metabolome, Metabolomics, Mice, Obesity, Recognition (Psychology), Weight Loss

Obesity, metabolic syndrome (MetS) and type 2 diabetes (T2D) are associated with decreased cognitive function. While weight loss and T2D remission result in improvements in metabolism and vascular function, it is less clear if these benefits extend to cognitive performance. Here, we highlight the malleable nature of MetS-associated cognitive dysfunction using a mouse model of high fat diet (HFD)-induced MetS. While learning and memory was generally unaffected in mice with type 1 diabetes (T1D), multiple cognitive impairments were associated with MetS, including deficits in novel object recognition, cued fear memory, and spatial learning and memory. However, a brief reduction in dietary fat content in chronic HFD-fed mice led to a complete rescue of cognitive function. Cerebral blood volume (CBV), a measure of vascular perfusion, was decreased during MetS, was associated with long term memory, and recovered following the intervention. Finally, repeated infusion of plasma collected from age-matched, low fat diet-fed mice improved memory in HFD mice, and was associated with a distinct metabolic profile. Thus, the cognitive dysfunction accompanying MetS appears to be amenable to treatment, related to cerebrovascular function, and mitigated by systemic factors.

Alternate JournalEBioMedicine
PubMed ID26870815
PubMed Central IDPMC4739422
Grant ListT32 DA007262 / DA / NIDA NIH HHS / United States
T32-ES07060 / ES / NIEHS NIH HHS / United States
F32 NS082017 / NS / NINDS NIH HHS / United States
P30ES000210 / ES / NIEHS NIH HHS / United States
T32 HL094294 / HL / NHLBI NIH HHS / United States
T32-HL094294 / HL / NHLBI NIH HHS / United States
S10RR027878 / RR / NCRR NIH HHS / United States
NIH R21AG043857 / AG / NIA NIH HHS / United States
S10 RR027878 / RR / NCRR NIH HHS / United States
NIDA T32DA007262 / / PHS HHS / United States
NIH F32NS082017 / NS / NINDS NIH HHS / United States
T32 ES007060 / ES / NIEHS NIH HHS / United States
P30 ES000210 / ES / NIEHS NIH HHS / United States