{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T20:29:39Z","timestamp":1778185779862,"version":"3.51.4"},"reference-count":26,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,4,29]],"date-time":"2022-04-29T00:00:00Z","timestamp":1651190400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Korea government (MSIT)","award":["NRF-2021R1F1A1059882"],"award-info":[{"award-number":["NRF-2021R1F1A1059882"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Nutrient availability and utilization in hypothalamic cells are directly associated with the regulation of whole-body energy homeostasis. Thus, establishing metabolic profiling in the hypothalamus in response to metabolic shift is valuable to better understand the underlying mechanism of appetite regulation. In the present study, we evaluate the alteration of lipophilic and hydrophilic metabolites in both the hypothalamus and serum of fasted mice. Fasted mice displayed an elevated ketone body and decreased lactate levels in the hypothalamus. In support of the metabolite data, we further confirmed that short-term food deprivation resulted in the altered expression of genes involved in cellular metabolic processes, including the shuttling of fuel sources and the production of monocarboxylates in hypothalamic astrocytes. Overall, the current study provides useful information to close the gap in our understanding of the molecular and cellular mechanisms underlying hypothalamic control of whole-body energy metabolism.<\/jats:p>","DOI":"10.3390\/metabo12050407","type":"journal-article","created":{"date-parts":[[2022,4,30]],"date-time":"2022-04-30T05:44:07Z","timestamp":1651297447000},"page":"407","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Metabolic Profiling of the Hypothalamus of Mice during Short-Term Food Deprivation"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9743-8513","authenticated-orcid":false,"given":"Ye Jin","family":"Kim","sequence":"first","affiliation":[{"name":"Division of Life Sciences, College of Life Sciences and Bioengineering, Incheon National University, Incheon 22012, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dasol","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Biological Science, University of Ulsan, Ulsan 44610, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hye Rim","family":"Yang","sequence":"additional","affiliation":[{"name":"Division of Life Sciences, College of Life Sciences and Bioengineering, Incheon National University, Incheon 22012, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6463-9645","authenticated-orcid":false,"given":"Byong Seo","family":"Park","sequence":"additional","affiliation":[{"name":"Division of Life Sciences, College of Life Sciences and Bioengineering, Incheon National University, Incheon 22012, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thai Hien","family":"Tu","sequence":"additional","affiliation":[{"name":"Division of Life Sciences, College of Life Sciences and Bioengineering, Incheon National University, Incheon 22012, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9361-8210","authenticated-orcid":false,"given":"Bora","family":"Jeong","sequence":"additional","affiliation":[{"name":"Department of Biological Science, University of Ulsan, Ulsan 44610, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Byung Ju","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Biological Science, University of Ulsan, Ulsan 44610, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2692-5370","authenticated-orcid":false,"given":"Jae Kwang","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Life Sciences, College of Life Sciences and Bioengineering, Incheon National University, Incheon 22012, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jae Geun","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Life Sciences, College of Life Sciences and Bioengineering, Incheon National University, Incheon 22012, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1016\/j.cmet.2011.08.016","article-title":"Brain Energy Metabolism: Focus on Astrocyte-Neuron Metabolic Cooperation","volume":"14","author":"Allaman","year":"2011","journal-title":"Cell Metab."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1017\/S0007114515000926","article-title":"Diet, nutrients and metabolism: Cogs in the wheel driving Alzheimer\u2019s disease pathology?","volume":"113","author":"Creegan","year":"2015","journal-title":"Br. J. Nutr."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.tins.2012.12.005","article-title":"Hypothalamic control of energy balance: Insights into the role of synaptic plasticity","volume":"36","author":"Dietrich","year":"2013","journal-title":"Trends Neurosci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.cell.2013.09.004","article-title":"Mitochondrial Dynamics Controlled by Mitofusins Regulate Agrp Neuronal Activity and Diet-Induced Obesity","volume":"155","author":"Dietrich","year":"2013","journal-title":"Cell"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1016\/j.cmet.2019.08.010","article-title":"Microglial UCP2 Mediates Inflammation and Obesity Induced by High-Fat Feeding","volume":"30","author":"Kim","year":"2019","journal-title":"Cell Metab."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"eabj2814","DOI":"10.1126\/sciadv.abj2814","article-title":"Astrocytic lipid metabolism determines susceptibility to diet-induced obesity","volume":"7","author":"Varela","year":"2021","journal-title":"Sci. Adv."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1016\/j.cell.2016.07.028","article-title":"Astrocytic Insulin Signaling Couples Brain Glucose Uptake with Nutrient Availability","volume":"166","author":"Quarta","year":"2016","journal-title":"Cell"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.bbrc.2019.03.047","article-title":"Linoleic acid rescues microglia inflammation triggered by saturated fatty acid","volume":"513","author":"Tu","year":"2019","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.tins.2010.12.001","article-title":"Astrocyte-neuron metabolic relationships: For better and for worse","volume":"34","author":"Allaman","year":"2011","journal-title":"Trends Neurosci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1038\/nn.3725","article-title":"Leptin signaling in astrocytes regulates hypothalamic neuronal circuits and feeding","volume":"17","author":"Kim","year":"2014","journal-title":"Nat. Neurosci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e144239","DOI":"10.1172\/JCI144239","article-title":"Hunger-promoting AgRP neurons trigger an astrocyte-mediated feed-forward autoactivation loop in mice","volume":"131","author":"Varela","year":"2021","journal-title":"J. Clin. Investig."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.bbrc.2021.04.043","article-title":"Enhanced lipid utilization is coupled to the sickness responses triggered by lipopolysaccharide","volume":"558","author":"Park","year":"2021","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1038\/s42255-019-0040-0","article-title":"Hypothalamic microglia as potential regulators of metabolic physiology","volume":"1","author":"Valdearcos","year":"2019","journal-title":"Nat. Metab."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1038\/nn.4274","article-title":"Agouti-related peptide neural circuits mediate adaptive behaviors in the starved state","volume":"19","author":"Padilla","year":"2016","journal-title":"Nat. Neurosci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"85","DOI":"10.2337\/db11-0857","article-title":"Hypothalamic leucine metabolism regulates liver glucose production","volume":"61","author":"Su","year":"2012","journal-title":"Diabetes"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/s00726-015-2067-1","article-title":"The role of leucine and its metabolites in protein and energy metabolism","volume":"48","author":"Duan","year":"2016","journal-title":"Amino Acids"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"21644","DOI":"10.1038\/s41598-021-00947-7","article-title":"Lactate activates hypothalamic POMC neurons by intercellular signaling","volume":"11","author":"Villar","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1016\/j.cmet.2019.08.004","article-title":"Tanycytes Regulate Lipid Homeostasis by Sensing Free Fatty Acids and Signaling to Key Hypothalamic Neuronal Populations via FGF21 Secretion","volume":"30","author":"Geller","year":"2019","journal-title":"Cell Metab."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1172\/JCI105621","article-title":"Studies in the ketosis of fasting","volume":"46","author":"Foster","year":"1967","journal-title":"J. Clin. Investig."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"E103","DOI":"10.1152\/ajpendo.00282.2015","article-title":"Evidence for hypothalamic ketone body sensing: Impact on food intake and peripheral metabolic responses in mice","volume":"310","author":"Carneiro","year":"2016","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1530\/JOE-11-0457","article-title":"The ketone body \u03b2-hydroxybutyric acid influences agouti-related peptide expression via AMP-activated protein kinase in hypothalamic GT1-7 cells","volume":"213","author":"Laeger","year":"2012","journal-title":"J. Endocrinol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3302","DOI":"10.1210\/jc.2012-1428","article-title":"Higher fasting plasma free fatty acid levels are associated with lower insulin secretion in children and adults and a higher incidence of type 2 diabetes","volume":"97","author":"Salgin","year":"2012","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Song, N., Jeong, D.Y., Tu, T.H., Park, B.S., Yang, H.R., Kim, Y.J., Kim, J.K., Park, J.T., Yeh, J.-Y., and Yang, S. (2021). Adiponectin Controls Nutrient Availability in Hypothalamic Astrocytes. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22041587"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1186\/s12974-020-01846-w","article-title":"Function of astrocyte MyD88 in high-fat-diet-induced hypothalamic inflammation","volume":"17","author":"Jin","year":"2020","journal-title":"J. Neuroinflamm."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"13939","DOI":"10.1073\/pnas.0907143106","article-title":"Cell-type-specific isolation of ribosome-associated mRNA from complex tissues","volume":"106","author":"Sanz","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Kim, Y.J., Tu, T.H., Yang, S., Kim, J.K., and Kim, J.G. (2020). Characterization of Fatty Acid Composition Underlying Hypothalamic Inflammation in Aged Mice. Molecules, 25.","DOI":"10.3390\/molecules25143170"}],"container-title":["Metabolites"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-1989\/12\/5\/407\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:04:37Z","timestamp":1760137477000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-1989\/12\/5\/407"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,29]]},"references-count":26,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2022,5]]}},"alternative-id":["metabo12050407"],"URL":"https:\/\/doi.org\/10.3390\/metabo12050407","relation":{},"ISSN":["2218-1989"],"issn-type":[{"value":"2218-1989","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,29]]}}}