Fibroblast growth factor 21 enhances learning and memory performance in mice by regulating hippocampal L-lactate homeostasis.
Int J Biol Macromol
; 271(Pt 2): 132667, 2024 Jun.
Article
en En
| MEDLINE
| ID: mdl-38801850
ABSTRACT
Fibroblast growth factor 21 (FGF21) is one endogenous metabolic molecule that functions as a regulator in glucose and lipid homeostasis. However, the effect of FGF21 on L-lactate homeostasis and its mechanism remains unclear until now. Forty-five Six-week-old male C57BL/6 mice were divided into three groups control, L-lactate, and FGF21 (1.5 mg/kg) groups. At the end of the treatment, nuclear magnetic resonance-based metabolomics, and key proteins related to L-lactate homeostasis were determined respectively to evaluate the efficacy of FGF21 and its mechanisms. The results showed that, compared to the vehicle group, the L-lactate-treated mice displayed learning and memory performance impairments, as well as reduced hippocampal ATP and NADH levels, but increased oxidative stress, mitochondrial dysfunction, and apoptosis, which suggesting inhibited L-lactate-pyruvate conversion in the brain. Conversely, FGF21 treatment ameliorated the L-lactate accumulation state, accompanied by restoration of the learning and memory defects, indicating enhanced L-lactate uptake and utilization in hippocampal neurons. We demonstrated that maintaining constant L-lactate-pyruvate flux is essential for preserving neuronal bioenergetic and redox levels. FGF21 contributed to preparing the brain for situations of high availability of L-lactate, thus preventing neuronal vulnerability in metabolic reprogramming.
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Banco de datos:
MEDLINE
Asunto principal:
Ácido Láctico
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Factores de Crecimiento de Fibroblastos
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Hipocampo
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Homeostasis
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Memoria
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Ratones Endogámicos C57BL
Límite:
Animals
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En
Año:
2024
Tipo del documento:
Article