{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T05:34:26Z","timestamp":1780378466897,"version":"3.54.1"},"reference-count":77,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,2,12]],"date-time":"2022-02-12T00:00:00Z","timestamp":1644624000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NIDDK-R01DK103746"],"award-info":[{"award-number":["NIDDK-R01DK103746"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>(1) Background: We previously demonstrated that disruption of IP6K1 improves metabolism, protecting mice from high-fat diet-induced obesity, insulin resistance, and non-alcoholic fatty liver disease and steatohepatitis. Age-induced metabolic dysfunction is a major risk factor for metabolic diseases. The involvement of IP6K1 in this process is unknown. (2) Methods: Here, we compared body and fat mass, insulin sensitivity, energy expenditure and serum-, adipose tissue- and liver-metabolic parameters of chow-fed, aged, wild type (aWT) and whole body Ip6k1 knockout (aKO) mice. (3) Results: IP6K1 was upregulated in the adipose tissue and liver of aWT mice compared to young WT mice. Moreover, Ip6k1 deletion blocked age-induced increase in body- and fat-weight and insulin resistance in mice. aKO mice oxidized carbohydrates more efficiently. The knockouts displayed reduced levels of serum insulin, triglycerides, and non-esterified fatty acids. Ip6k1 deletion partly protected age-induced decline of the thermogenic uncoupling protein UCP1 in inguinal white adipose tissue. Targets inhibited by IP6K1 activity such as the insulin sensitivity- and energy expenditure-inducing protein kinases, protein kinase B (PKB\/Akt) and AMP-activated protein kinase (AMPK), were activated in the adipose tissue and liver of aKO mice. (4) Conclusions: Ip6k1 deletion maintains healthy metabolism in aging and thus, targeting this kinase may delay the development of age-induced metabolic dysfunction.<\/jats:p>","DOI":"10.3390\/ijms23042059","type":"journal-article","created":{"date-parts":[[2022,2,13]],"date-time":"2022-02-13T21:08:43Z","timestamp":1644786523000},"page":"2059","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Whole Body Ip6k1 Deletion Protects Mice from Age-Induced Weight Gain, Insulin Resistance and Metabolic Dysfunction"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1089-084X","authenticated-orcid":false,"given":"Sarbani","family":"Ghoshal","sequence":"first","affiliation":[{"name":"Department of Metabolism and Aging, The Scripps Research Institute, Jupiter, FL 33458, USA"},{"name":"Department of Biological Sciences and Geology, QCC-City University of New York, New York, NY 11364, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandip","family":"Mukherjee","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Physiology, Saint Louis University School of Medicine, Saint Louis, MO 63104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Molee","family":"Chakraborty","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Physiology, Saint Louis University School of Medicine, Saint Louis, MO 63104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eliwaza Naomi","family":"Msengi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Physiology, Saint Louis University School of Medicine, Saint Louis, MO 63104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jake","family":"Haubner","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Physiology, Saint Louis University School of Medicine, Saint Louis, MO 63104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anutosh","family":"Chakraborty","sequence":"additional","affiliation":[{"name":"Department of Metabolism and Aging, The Scripps Research Institute, Jupiter, FL 33458, USA"},{"name":"Department of Pharmacology and Physiology, Saint Louis University School of Medicine, Saint Louis, MO 63104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,12]]},"reference":[{"key":"ref_1","unstructured":"Feingold, K.R., Anawalt, B., Boyce, A., Chrousos, G., de Herder, W.W., Dhatariya, K., Dungan, K., Grossman, A., Hershman, J.M., and Hofland, J. 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