{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T10:31:57Z","timestamp":1761647517941,"version":"build-2065373602"},"reference-count":31,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T00:00:00Z","timestamp":1761523200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"R01 Awards from NIDDK","award":["DK110439","DK132643"],"award-info":[{"award-number":["DK110439","DK132643"]}]},{"name":"P20 Award","award":["GM121176","GM130422"],"award-info":[{"award-number":["GM121176","GM130422"]}]},{"DOI":"10.13039\/100000968","name":"Postdoc Fellowship Awards from American Heart Association","doi-asserted-by":"publisher","award":["20POST35120020"],"award-info":[{"award-number":["20POST35120020"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Start-up research grants from Hunan Normal University","award":["0531120","0531320"],"award-info":[{"award-number":["0531120","0531320"]}]},{"name":"Dedicated Health Research Funds provided by the University of New Mexico School of Medicine"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Intermittent fasting (IF) has emerged as a promising strategy for managing obesity and related metabolic disorders. Although metabolic adaptations in adipose tissue during IF are well documented, the specific reprogramming of white adipose tissue (WAT) under prolonged cycles of fasting and refeeding remains incompletely understood. Using mass spectrometry-based approaches, including liquid chromatography (LC) and capillary electrophoresis (CE), we identified a marked increase in inositol monophosphates (InsP1s) in obese adipose tissue following extended IF. Specifically, myo-inositol-1-phosphate and myo-inositol-3-phosphate, which are typically present at low levels in gonadal WAT (gWAT) of diet-induced obese mice, were significantly elevated after 15 cycles of IF. Additionally, extended IF upregulated the expression levels of inositol tetrakisphosphate 1-kinase (ITPK1) and inositol monophosphatase 1 (IMPA1), two key enzymes involved in InsP1 metabolism. These increases coincide with reductions in body weight and fat mass, as well as improved insulin sensitivity. This reprogramming was further supported by enhanced tricarboxylic acid (TCA) cycle activity. Collectively, these findings suggest the inositol monophosphate pathway as a novel mechanism underlying fasting-induced metabolic adaptation in adipose tissue and highlight the potential of these metabolites as biomarkers for obesity and related metabolic conditions.<\/jats:p>","DOI":"10.3390\/biom15111514","type":"journal-article","created":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T09:16:07Z","timestamp":1761642967000},"page":"1514","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Adipose Inositol Monophosphate Metabolism Is Associated with Fasting Regimen-Elicited Metabolic Benefits"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2811-7230","authenticated-orcid":false,"given":"Chunqing","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA"},{"name":"Autophagy Inflammation and Metabolism Center for Biomedical Research Excellence, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bilian","family":"Liu","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Metabolic Diseases, Key Laboratory of Cardiometabolic Medicine of Hunan Province, Metabolic Syndrome Research Center, The Second Xiangya Hospital of Central South University, Changsha 410081, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xi","family":"Chen","sequence":"additional","affiliation":[{"name":"The National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, Hunan Normal University, Changsha 410081, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuo","family":"Wang","sequence":"additional","affiliation":[{"name":"The National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, Hunan Normal University, Changsha 410081, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5877-627X","authenticated-orcid":false,"given":"Xing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA"},{"name":"The National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, Hunan Normal University, Changsha 410081, China"},{"name":"Hunan Provincial Key Laboratory of Animal Intestinal Function and Regulation, College of Life Science, Hunan Normal University, Changsha 410081, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1639-262X","authenticated-orcid":false,"given":"Meilian","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA"},{"name":"Autophagy Inflammation and Metabolism Center for Biomedical Research Excellence, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/0047-6374(90)90107-Q","article-title":"Effects of intermittent feeding upon body weight and lifespan in inbred mice: Interaction of genotype and age","volume":"55","author":"Goodrick","year":"1990","journal-title":"Mech. Ageing Dev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"6216","DOI":"10.1073\/pnas.1035720100","article-title":"Intermittent fasting dissociates beneficial effects of dietary restriction on glucose metabolism and neuronal resistance to injury from calorie intake","volume":"100","author":"Anson","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.jnutbio.2008.11.001","article-title":"Improvements in body fat distribution and circulating adiponectin by alternate-day fasting versus calorie restriction","volume":"21","author":"Varady","year":"2010","journal-title":"J. Nutr. Biochem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1016\/j.cmet.2017.08.019","article-title":"Intermittent Fasting Promotes White Adipose Browning and Decreases Obesity by Shaping the Gut Microbiota","volume":"26","author":"Li","year":"2017","journal-title":"Cell Metab."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1038\/cr.2017.126","article-title":"Intermittent fasting promotes adipose thermogenesis and metabolic homeostasis via VEGF-mediated alternative activation of macrophage","volume":"27","author":"Kim","year":"2017","journal-title":"Cell Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1038\/s41467-017-00178-3","article-title":"Every-other-day feeding extends lifespan but fails to delay many symptoms of aging in mice","volume":"8","author":"Xie","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1210\/en.2018-00701","article-title":"Intermittent Fasting Improves Glucose Tolerance and Promotes Adipose Tissue Remodeling in Male Mice Fed a High-Fat Diet","volume":"160","author":"Liu","year":"2019","journal-title":"Endocrinology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"108804","DOI":"10.1016\/j.celrep.2021.108804","article-title":"Proteomics analysis of adipose depots after intermittent fasting reveals visceral fat preservation mechanisms","volume":"34","author":"Harney","year":"2021","journal-title":"Cell Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e153755","DOI":"10.1172\/jci.insight.153755","article-title":"Adipocyte-derived PGE2 is required for intermittent fasting-induced Treg proliferation and improvement of insulin sensitivity","volume":"7","author":"Wang","year":"2022","journal-title":"JCI Insight"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1038\/s41467-024-45724-y","article-title":"Adipocyte p53 coordinates the response to intermittent fasting by regulating adipose tissue immune cell landscape","volume":"15","author":"Reinisch","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"RP91060","DOI":"10.7554\/eLife.91060","article-title":"Intermittent fasting promotes type 3 innate lymphoid cells secreting IL-22 contributing to the beigeing of white adipose tissue","volume":"12","author":"Chen","year":"2024","journal-title":"Elife"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.cell.2024.11.004","article-title":"Intermittent fasting triggers interorgan communication to suppress hair follicle regeneration","volume":"188","author":"Chen","year":"2025","journal-title":"Cell"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1038\/s41586-022-04884-x","article-title":"The gut metabolite indole-3 propionate promotes nerve regeneration and repair","volume":"607","author":"Serger","year":"2022","journal-title":"Nature"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3180","DOI":"10.1016\/j.celrep.2018.08.055","article-title":"Adipose mTORC1 Suppresses Prostaglandin Signaling and Beige Adipogenesis via the CRTC2-COX-2 Pathway","volume":"24","author":"Zhang","year":"2018","journal-title":"Cell Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1038\/35073015","article-title":"Back in the water: The return of the inositol phosphates","volume":"2","author":"Irvine","year":"2001","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.1016\/j.cell.2010.11.045","article-title":"SnapShot: Inositol phosphates","volume":"143","author":"Hatch","year":"2010","journal-title":"Cell"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Tu-Sekine, B., and Kim, S.F. (2022). The Inositol Phosphate System-A Coordinator of Metabolic Adaptability. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23126747"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Chatree, S., Thongmaen, N., Tantivejkul, K., Sitticharoon, C., and Vucenik, I. (2020). Role of Inositols and Inositol Phosphates in Energy Metabolism. Molecules, 25.","DOI":"10.3390\/molecules25215079"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1126\/science.1211908","article-title":"Influence of inositol pyrophosphates on cellular energy dynamics","volume":"334","author":"Szijgyarto","year":"2011","journal-title":"Science"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1400","DOI":"10.1038\/s42255-021-00468-7","article-title":"5-IP(7) is a GPCR messenger mediating neural control of synaptotagmin-dependent insulin exocytosis and glucose homeostasis","volume":"3","author":"Zhang","year":"2021","journal-title":"Nat. Metab."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1016\/j.cell.2010.11.032","article-title":"Inositol pyrophosphates inhibit Akt signaling, thereby regulating insulin sensitivity and weight gain","volume":"143","author":"Chakraborty","year":"2010","journal-title":"Cell"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"24551","DOI":"10.1073\/pnas.1911431116","article-title":"ITPK1 mediates the lipid-independent synthesis of inositol phosphates controlled by metabolism","volume":"116","author":"Wilson","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"33","DOI":"10.4252\/wjsc.v6.i1.33","article-title":"Distinction of white, beige and brown adipocytes derived from mesenchymal stem cells","volume":"6","author":"Park","year":"2014","journal-title":"World J. Stem Cells"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"E945","DOI":"10.1152\/ajpendo.00473.2013","article-title":"Brown and white adipose tissues: Intrinsic differences in gene expression and response to cold exposure in mice","volume":"306","author":"Rosell","year":"2014","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1093\/cvr\/cvae017","article-title":"Depleting inositol pyrophosphate 5-InsP7 protected the heart against ischaemia-reperfusion injury by elevating plasma adiponectin","volume":"120","author":"Fu","year":"2024","journal-title":"Cardiovasc. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1038\/s42255-023-00945-1","article-title":"Depletion of JunB increases adipocyte thermogenic capacity and ameliorates diet-induced insulin resistance","volume":"6","author":"Zhang","year":"2024","journal-title":"Nat. Metab."},{"key":"ref_27","first-page":"1145","article-title":"Vitamin E: Function and metabolism","volume":"13","author":"Traber","year":"1999","journal-title":"FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2060","DOI":"10.1038\/s41467-022-29589-7","article-title":"Gut microbiota-bile acid crosstalk contributes to the rebound weight gain after calorie restriction in mice","volume":"13","author":"Li","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"S18","DOI":"10.3177\/jnsv.65.S18","article-title":"Anticancer Properties of Inositol Hexaphosphate and Inositol: An Overview","volume":"65","author":"Vucenik","year":"2019","journal-title":"J. Nutr. Sci. Vitaminol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e001989","DOI":"10.1136\/openhrt-2022-001989","article-title":"Myo-inositol for insulin resistance, metabolic syndrome, polycystic ovary syndrome and gestational diabetes","volume":"9","author":"DiNicolantonio","year":"2022","journal-title":"Open Heart"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1987","DOI":"10.1194\/jlr.R071712","article-title":"A short history of inositol lipids","volume":"57","author":"Irvine","year":"2016","journal-title":"J. Lipid Res."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/11\/1514\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T10:27:50Z","timestamp":1761647270000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/11\/1514"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,27]]},"references-count":31,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["biom15111514"],"URL":"https:\/\/doi.org\/10.3390\/biom15111514","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,27]]}}}