Metabolic profiling in the hypothalamus of aged mice

Metabolic abnormalities are tightly connected to the perturbation of normal brain functions, thereby causing multiple neurodegenerative diseases. The hypothalamus is the master unit that controls the whole-body energy homeostasis. Thus, altered metabolic activity in the hypothalamus could be a crucial clue to better understand the development of metabolic disorders during aging. The current study aimed to investigate the changes in hypothalamic metabolites according to the aging process using gas chromatography-mass spectrometry. We identified that multiple metabolites and neurotransmitters were effectively reduced in the hypothalamus of aged mice. In addition, we observed increased levels of genes linked to the production and utilization of monocarboxylates in the aged hypothalamus, indicating the initiation of metabolic activity to produce alternative nutrient sources. Lastly, we found a reduced number of astrocytes in the hypothalamus of aged mice, suggesting that reduced nutrient availability in the hypothalamus might be associated with the decreased activity of astrocytes during aging. Collectively, the present study suggests that the deterioration of metabolic activities in the hypothalamus might be a primary cause and/or outcome of metabolic diseases associated with the aging process. (c) 2022 Elsevier Inc. All rights reserved.

Automated summary

This study used gas chromatography-mass spectrometry to investigate changes in hypothalamic metabolites during the aging process. The results showed a significant decrease in multiple metabolites and neurotransmitters in the hypothalamus of aged mice. Additionally, there was an increase in genes related to monocarboxylate production and utilization, indicating metabolic activity to produce alternative nutrient sources. Reduced astrocyte activity and nutrient availability in the hypothalamus were also observed in aged mice. Overall, this study suggests that metabolic dysfunction in the hypothalamus may be a primary cause and/or outcome of age-related metabolic diseases.