{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T13:52:21Z","timestamp":1776433941223,"version":"3.51.2"},"reference-count":25,"publisher":"American Diabetes Association","issue":"6","license":[{"start":{"date-parts":[[2024,3,19]],"date-time":"2024-03-19T00:00:00Z","timestamp":1710806400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.diabetesjournals.org\/journals\/pages\/license"}],"funder":[{"name":"NIH","award":["K01 DK135924"],"award-info":[{"award-number":["K01 DK135924"]}]},{"name":"NIH","award":["P30 CA068485"],"award-info":[{"award-number":["P30 CA068485"]}]},{"name":"NIH","award":["P30 DK020593"],"award-info":[{"award-number":["P30 DK020593"]}]},{"name":"NIH","award":["R01 DK106348"],"award-info":[{"award-number":["R01 DK106348"]}]},{"name":"NIH","award":["S10 OD025199"],"award-info":[{"award-number":["S10 OD025199"]}]},{"name":"NIH","award":["T32 DK101003"],"award-info":[{"award-number":["T32 DK101003"]}]},{"name":"NIH","award":["U01 CA235508"],"award-info":[{"award-number":["U01 CA235508"]}]},{"name":"NIH","award":["U24 DK059637"],"award-info":[{"award-number":["U24 DK059637"]}]},{"name":"NIH","award":["U2C DK135073"],"award-info":[{"award-number":["U2C DK135073"]}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,6,1]]},"abstract":"<jats:sec>\n                  <jats:title\/>\n                  <jats:p>Diabetes and obesity are risk factors for kidney disease. Whereas renal glucose production increases in diabetes, recent data suggest that gluconeogenic and oxidative capacity decline in kidney disease. Thus, metabolic dysregulation caused by diet-induced insulin resistance may sensitize the kidney for a loss in function. Here, we examined how diet-induced insulin resistance disrupts mitochondrial metabolic fluxes in the renal cortex in\u00a0vivo. C57BL\/6J mice were rendered insulin resistant through high-fat (HF) feeding; anaplerotic, cataplerotic, and oxidative metabolic fluxes in the cortex were quantified through 13C-isotope tracing during a hyperinsulinemic-euglycemic clamp. As expected, HF-fed mice exhibited increased body weight, gluconeogenesis, and systemic insulin resistance compared with chow-fed mice. Relative to the citric acid cycle, HF feeding increased metabolic flux through pyruvate carboxylation (anaplerosis) and phosphoenolpyruvate carboxykinase (cataplerosis) and decreased flux through the pyruvate dehydrogenase complex in the cortex. Furthermore, the relative flux from nonpyruvate sources of acetyl-CoA profoundly increased in the cortex of HF-fed mice, correlating with a marker of oxidative stress. The data demonstrate that HF feeding spares pyruvate from dehydrogenation at the expense of increasing cataplerosis, which may underpin renal gluconeogenesis during insulin resistance; the results also support the hypothesis that dysregulated oxidative metabolism in the kidney contributes to metabolic disease.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Article Highlights<\/jats:title>\n               <\/jats:sec>","DOI":"10.2337\/db23-0710","type":"journal-article","created":{"date-parts":[[2024,3,19]],"date-time":"2024-03-19T18:29:11Z","timestamp":1710872951000},"page":"903-908","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":3,"title":["Metabolic Fluxes in the Renal Cortex Are Dysregulated In\u00a0Vivo in Response to High-Fat Diet"],"prefix":"10.2337","volume":"73","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9887-0922","authenticated-orcid":false,"given":"Clinton M.","family":"Hasenour","sequence":"first","affiliation":[{"name":"1Department of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0750-5138","authenticated-orcid":false,"given":"Deveena R.","family":"Banerjee","sequence":"additional","affiliation":[{"name":"2Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jamey D.","family":"Young","sequence":"additional","affiliation":[{"name":"1Department of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN"},{"name":"2Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, 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