Abstract Summary/Description
High fat consumption is detrimental for brain health and cognition. Fibroblast growth factor 21 (FGF21) is elevated in response to an HFD. Administration of FGF21 improves central health in preclinical models. The role of endogenous FGF21 in protecting the brain against an HFD remains unexplored. This study aimed to identify whether endogenous FGF21 aids in protecting the brain against HFD-induced cognitive impairments and brain dysfunction in both sexes. Male and female wild-type (WT) and FGF21 knockout (Fgf21-/-) mice followed a chow (13.6% fat) or HFD (60% fat) for 9 weeks (n = 7-8, diet x genotype x sex). Body weight was measured weekly. Serum FGF21 was measured by ELISA. Cognition was assessed by novel object recognition test, Barnes maze, and fear conditioning. Protein was isolated from whole brain and hippocampus and was measured by western blot. HFD feeding increased body weight of all mice and increased FGF21 in WT mice. HFD decreased recognition memory of WT mice, while recognition memory was decreased in Fgf21-/- mice independent of diet(s). HFD impaired spatial learning and memory of WT males. HFD had no effect on associative cognition, regardless of sex and Fgf21-/- mice spent more time frozen overall. HFD increased SIRT1 and NOX2 in the brain of WT males, but not females. Whereas IBA1 was elevated in the hippocampus of WT males only. Our data suggest that increased endogenous FGF21 in response to HFD intake does not protect against HFD-induced cognitive impairments or brain dysfunction.
