Abstract
Obesity impacts brain metabolism and function, and constitutes a risk factor for dementia development. Long-term exposure to obesogenic diets leads to taurine accumulation in the hippocampus of rodents. Taurine has putative beneficial effects on cell homeostasis, and is reported to improve cognition. Therefore, hippocampal taurine accumulation in obese and diabetic models might constitute a counteracting response to metabolic stress. This study tested the hypothesis that treatment with taurine or with N-acetylcysteine (NAC), which provides cysteine for the synthesis of taurine and the antioxidant glutathione, prevent obesity-associated hippocampal alterations and memory impairment. Female mice were fed either a regular diet or a high-fat diet (HFD). For the same period, some mice had access to 3%(w/v) taurine or 3%(w/v) NAC in the drinking water. After 2 months, magnetic resonance spectroscopy was used to measure metabolite profiles. Then, memory was assessed in novel object and novel location recognition tests. HFD feeding caused memory impairment in both tests, and reduced concentration of lactate, phosphocreatine-to-creatine ratio, and the neuronal marker N-acetylaspartate in the hippocampus. Both taurine and NAC prevented HFD-induced memory impairment and N-acetylaspartate reduction. NAC, but not taurine, prevented the HFD-induced reduction of lactate and phosphocreatine-to-creatine ratio. Analysis of the metabolite profile further revealed prominent NAC/taurine-induced increase of glutamate and GABA levels in the hippocampus. We conclude that NAC and taurine prevent of neuronal dysfunction, while only NAC prevents energy metabolism dysregulation in HFD-induced obesity in female mice.
Competing Interest Statement
The authors have declared no competing interest.
Abbreviations
- AD
- Alzheimer’s disease
- Aβ
- amyloid β
- CD
- control diet
- CDO1
- cysteine dioxygenase 1
- CSAD
- cysteine sulfinic acid decarboxylase
- GAT-2
- GABA transporter 2
- HFD
- high-fat diet
- HFHSD
- high-fat and high-sucrose diet
- MRS
- magnetic resonance spectroscopy
- NAC
- N-acetylcysteine
- NLR
- novel location recognition
- NMR
- Nuclear magnetic resonance
- NOR
- novel object recognition
- PBS
- phosphate-buffered saline
- T2D
- type 2 diabetes
- TauT
- taurine transporter
- VOI
- volume of interest