https://scholar.dgist.ac.kr/handle/20.500.11750/289 Sat, 04 Apr 2026 14:57:47 GMT 2026-04-04T14:57:47Z https://scholar.dgist.ac.kr/handle/20.500.11750/59920 Title: Threonic acid, an ascorbic acid metabolite, synergizes with intermittent fasting to ameliorate obesity Author(s): Oh, Sungjoon; Park, Seokjae; Kim, Eun-Kyoung Abstract: Intermittent fasting (IF) is a safe and sustainable approach for obesity treatment, yet its weight loss efficacy is relatively modest compared with that of pharmacologic anti-obesity therapies. The synergistic benefits of pairing IF with administration of nutrient-derived metabolites remain poorly understood. Here we report that combining IF with threonic acid (TA), an ascorbic acid metabolite, led to more pronounced reductions in body weight and food intake, as well as improvements in energy expenditure and glycemic control, compared with either intervention alone in diet-induced obese mice. These metabolic benefits were associated with the anorexigenic role of TA in reversing fasting-induced upregulation of the hypothalamic orexigenic neuropeptides NPY and AGRP. In the hypothalamus, TA competed with glucose for uptake via glucose transporter 3 (GLUT3), while IF boosted the TA uptake through both glucose depletion and upregulation of GLUT3, resulting in a more robust suppression of NPY and AGRP expression. Collectively, our findings highlight the combination of TA with IF as a promising metabolite-based combinatorial strategy to enhance the therapeutic efficacy of obesity treatment. Wed, 31 Dec 2025 15:00:00 GMT https://scholar.dgist.ac.kr/handle/20.500.11750/59920 2025-12-31T15:00:00Z https://scholar.dgist.ac.kr/handle/20.500.11750/58519 Title: ATP stimulates appetite by enhancing the expression of hypothalamic orexigenic neuropeptides Author(s): Kim, Nayoun; Kim, Eun-Kyoung Abstract: Hypothalamic neuropeptides play a pivotal role in regulating appetite and energy homeostasis. Extracellular ATP, a key signaling molecule in the hypothalamus, is associated with neuronal activity and metabolic processes. However, its role in appetite control remains unclear. This study explored how sustained extracellular ATP regulates the expression of hypothalamic orexigenic neuropeptides Agrp and Npy. The administration of ATP alone reduced food intake, body weight, and orexigenic neuropeptide expression in mice. Conversely, inhibition of ATP conversion into AMP using the ectonucleoside triphosphate diphosphohydrolase inhibitor ARL67156 caused a transient increase in these parameters. Prolonged extracellular ATP was shown to upregulate Agrp and Npy expression via purinergic P2X4 receptor (P2X4R) activation in AGRP/NPY-expressing cells. Activation of P2X4R induced CaMKII phosphorylation, which subsequently led to CREB phosphorylation and upregulation of orexigenic neuropeptides. Our findings reveal a mechanism whereby extracellular ATP accumulation promotes appetite through P2X4R-CaMKII-CREB signaling, shedding light on how extracellular ATP impacts hypothalamic appetite control. © The Author(s) 2025. Sat, 31 May 2025 15:00:00 GMT https://scholar.dgist.ac.kr/handle/20.500.11750/58519 2025-05-31T15:00:00Z https://scholar.dgist.ac.kr/handle/20.500.11750/58446 Title: Adenosine transmission from hypothalamic tanycytes to AGRP/NPY neurons regulates energy homeostasis Author(s): Kim, Nayoun; Kim, Seolsong; Park, Seokjae; Kim, Eun-Kyoung Abstract: Tanycytes are a pivotal component of the hypothalamic network that controls energy homeostasis. Despite their importance, the regulatory mechanisms governing tanycyte–neuron interactions in response to metabolic signals remain unexplored. Here we report that adenosine signaling between tanycytes and AGRP/NPY neurons is crucial for tanycytic metabolic regulation mediated by translocator protein 18 kDa (TSPO). Tanycyte-specific Tspo-knockout mice displayed reduced food consumption and weight loss associated with the downregulation of Agrp and Npy expression under high-fat diet feeding. Tspo-deficient tanycytes had elevated levels of intracellular ATP, which was released via connexin 43 hemichannels and extracellularly converted into adenosine by tanycytic ectonucleotidases. The adenosine signal was perceived by adenosine A1 receptors on adjacent AGRP/NPY neurons, reducing ERK phosphorylation, which in turn downregulated Agrp and Npy expression. Our findings underscore the anorexic role of adenosine as a gliotransmitter in the intricate communication between tanycytes and neurons for regulating appetite and body weight. (Figure presented.) © The Author(s) 2025. Wed, 30 Apr 2025 15:00:00 GMT https://scholar.dgist.ac.kr/handle/20.500.11750/58446 2025-04-30T15:00:00Z https://scholar.dgist.ac.kr/handle/20.500.11750/57383 Title: Machine Learning-Based Plasma Metabolomics in Liraglutide-Treated Type 2 Diabetes Mellitus Patients and Diet-Induced Obese Mice Author(s): Park, Seokjae; Kim, Eun-Kyoung Abstract: Liraglutide, a glucagon-like peptide-1 receptor agonist, is effective in the treatment of type 2 diabetes mellitus (T2DM) and obesity. Despite its benefits, including improved glycemic control and weight loss, the common metabolic changes induced by liraglutide and correlations between those in rodents and humans remain unknown. Here, we used advanced machine learning techniques to analyze the plasma metabolomic data in diet-induced obese (DIO) mice and patients with T2DM treated with liraglutide. Among the machine learning models, Support Vector Machine was the most suitable for DIO mice, and Gradient Boosting was the most suitable for patients with T2DM. Through the cross-evaluation of machine learning models, we found that liraglutide promotes metabolic shifts and interspecies correlations in these shifts between DIO mice and patients with T2DM. Our comparative analysis helped identify metabolic correlations influenced by liraglutide between humans and rodents and may guide future therapeutic strategies for T2DM and obesity. © 2024 by the authors. Sat, 31 Aug 2024 15:00:00 GMT https://scholar.dgist.ac.kr/handle/20.500.11750/57383 2024-08-31T15:00:00Z