Metabolic clues to memory loss: High-fat diets and brain-adipose crosstalk in zebrafish

Obesity is a growing public health concern that significantly impacts cognitive functions, including memory. This research explores how a high-fat diet affects short-term memory, employing the novel object recognition (NOR) test and NMR-based metabolomics to elucidate metabolic alterations in the brain and adipose tissue. The zebrafish were divided into two groups: one receiving a standard diet (SD) and the other a high-fat diet (HFD). Body mass index (BMI) was assessed every two weeks for a period of eight weeks. The NOR test was used to determine the discrimination index (DI) for evaluating the short-term memory of the SD and HFD groups. NMR spectroscopy was employed to investigate the metabolites in brain and adipose tissues, and multivariate data analysis was conducted to discover significant metabolic alterations. The high-fat diet (HFD) resulted in a significant increase in body mass index (BMI) (p < 0.0001) compared to the standard diet (SD) group from week 4 to week 8. A significant reduction in the discrimination index (24.95 %) in the HFD group against the SD group suggests a decline in memory performance among HFD subjects. NMR-based metabolomics of adipose tissue revealed that linoleic acid and caprylic acid were consistently found to exhibit increased levels in the HFD group across all assessments, whereas lauric acid, ALA, EPA, and DHA were consistently present at elevated levels in the adipose tissue of the SD group. NMR-based metabolomics of the brain identified GABA, taurine, and histamine as the key metabolites distinguishing the HFD from the SD group in female zebrafish. For male zebrafish brains, taurine, phenylalanine, and tryptophan were identified as the most significant metabolites for differentiating between HFD and SD. These metabolites demonstrated a notable decrease in the HFD group relative to the SD group. The results of this study align with those of previously reported studies in rodents and humans, indicating that memory impairment associated with obesity may stem from neuroinflammation and changes in synaptic plasticity. This research provides insights into the molecular changes in adipose tissue and the brain that occur when individuals receive a high-fat diet (HFD), which may enhance our understanding of the link between obesity and memory impairment, ultimately leading to a better comprehension of the disease.