{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T04:46:28Z","timestamp":1785732388993,"version":"3.56.0"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T00:00:00Z","timestamp":1785715200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01 HL176793A, T32 HL155011-01A1, F31 HL165858"],"award-info":[{"award-number":["R01 HL176793A, T32 HL155011-01A1, F31 HL165858"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Obesity-induced ectopic lipid accumulation inside skeletal muscle (SKM) (myosteatosis) and the liver (hepatosteatosis) contributes to local metabolic dysfunction and serves as a launchpad for the progression of diabetes. While stearoyl-CoA desaturase 1 (SCD1), an ER-bound enzyme that catalyzes the rate-limiting step in monounsaturated fatty acid (MUFA) synthesis, is widely recognized as a lynchpin facilitator of steatosis, much controversy exists on its efficacy as a therapeutic target. In particular, a total lack of SKM-specific SCD1 KO models has greatly limited our understanding of SCD1-mediated myosteatosis\u2019 relative contribution to metabolic syndrome.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Global SCD1 knockout mice bred on the leptin receptor mutant (db\/db) background (db\/SCD1 mice) and SKM-specific inducible ACTA1-cre mice bred on the SCD1\n                      <jats:sup>fl\/fl<\/jats:sup>\n                      background overexpressing agouti-related peptide (AgRP) had their body\/tissue composition analyzed via nuclear magnetic resonance (NMR) spectrometry. Insulin-mediated metabolism was analyzed by screening blood\/plasma for related metabolites. Lastly, we performed RT-qPCR to screen target metabolic genes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Global SCD1 deletion in db\/db mice reduced weight gain and steatosis, leading to pathological liver remodeling and severe diabetes. Next, we found that SKM-restricted SCD1 deletion in adult mice with established obesity increased AgRP-induced weight gain while preserving whole-body fat composition. SKM SCD1 KO led to reduced myosteatosis while exacerbating hepatosteatosis and indices of insulin insensitivity. Whereas SKM responded to lack of myocellular SCD1 by inhibiting expression of trans-endothelial fatty acid chaperone FABP4, hepatosteatosis coincided with upregulation of SCD1 and downregulation of master regulator of fatty acid oxidation (FAO) PPAR\u03b1 in the liver.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Loss of peripheral leptin-mediated FAO and SCD1-regulated lipid storage act synergistically to exacerbate hyperlipidemia, hyperglycemia, and multi-organ quality decline, collectively promoting systemic inflammation and diabetes progression. Interestingly, AgRP mice adapt to selective inhibition of SCD1-mediated myosteatosis by expanding hepatosteatosis and precipitating metabolic syndrome. Gene expression data imply SCD1-KO\u2013mediated impaired SKM lipid flux inhibits liver lipid metabolism in favor of storage. These results indicate a potent link between intramyocellular lipid storage capacity and the progression of metabolic-associated fatty liver disease.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphys.2026.1826756","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T04:28:16Z","timestamp":1785731296000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Myofiber stearoyl-CoA desaturase 1 moderates MAFLD and metabolic syndrome in obese mice"],"prefix":"10.3389","volume":"17","author":[{"given":"Andrew","family":"Guilfoyle-Speese","sequence":"first","affiliation":[{"name":"Vascular Biology Center, Medical College of Georgia, Augusta University","place":["Augusta, GA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cody","family":"Bridgewater","sequence":"additional","affiliation":[{"name":"Vascular Biology Center, Medical College of Georgia, Augusta University","place":["Augusta, GA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caleb","family":"Padgett","sequence":"additional","affiliation":[{"name":"Vascular Biology Center, Medical College of Georgia, Augusta University","place":["Augusta, GA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hunter","family":"Sellars","sequence":"additional","affiliation":[{"name":"Vascular Biology Center, Medical College of Georgia, Augusta University","place":["Augusta, GA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Mintz","sequence":"additional","affiliation":[{"name":"Vascular Biology Center, Medical College of Georgia, Augusta University","place":["Augusta, GA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Fulton","sequence":"additional","affiliation":[{"name":"Vascular Biology Center, Medical College of Georgia, Augusta University","place":["Augusta, GA, United States"]},{"name":"Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta University","place":["Augusta, GA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Stepp","sequence":"additional","affiliation":[{"name":"Vascular Biology Center, Medical College of Georgia, Augusta University","place":["Augusta, GA, United States"]},{"name":"Department of Physiology, Medical College of Georgia, Augusta University","place":["Augusta, GA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"15761","DOI":"10.1038\/s41598-019-52339-7","article-title":"Hepatic stearoyl-CoA desaturase-1 deficiency-mediated activation of mTORC1- PGC-1alpha axis regulates ER stress during high-carbohydrate feeding","volume":"9","author":"Aljohani","year":"2019","journal-title":"Sci. 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