{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T13:22:23Z","timestamp":1781270543190,"version":"3.54.1"},"reference-count":31,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,11,4]],"date-time":"2021-11-04T00:00:00Z","timestamp":1635984000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Alabama in Huntsville, USA","award":["251359"],"award-info":[{"award-number":["251359"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>The liver plays a key role in whole-body, glucose and lipid homeostasis. Nutritional signals in response to fasting and refeeding regulate hepatic lipid synthesis. It is established that activation of mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1) in response to overnutrition regulates MAPK-dependent pathways that control lipid metabolism in the liver. However, the regulatory mechanisms and the impact of the actions of MKP-1 in hepatic response to fasting remains unclear. We investigated the effect of fasting on the expression of MKP-1 and the impact on hepatic response to feeding. In this study, we demonstrate that fasting stress induced upregulation of hepatic MKP-1 protein levels with a corresponding downregulation of p38 MAPK and JNK phosphorylation in mouse livers. We found that MKP-1-deficient livers are resistant to fasting-induced hepatic steatosis. Hepatic MKP-1 deficiency impaired fasting-induced changes in the levels of key transcription factors involved in the regulation of fatty acid and cholesterol metabolism including Srebf2 and Srebf1c. Mechanistically, MKP-1 negatively regulates Srebf2 expression by attenuating p38 MAPK pathway, suggesting its contribution to the metabolic effects of MKP-1 deficiency in the fasting liver. These findings support the hypothesis that upregulation of MKP-1 is a physiological relevant response and might be beneficial in hepatic lipid utilization during fasting in the liver. Collectively, these data unravel some of the complexity and tissue specific interaction of MKP-1 action in response to changes in nutritional cues, including fasting and excess nutrients<\/jats:p>","DOI":"10.3390\/nu13113941","type":"journal-article","created":{"date-parts":[[2021,11,4]],"date-time":"2021-11-04T22:25:54Z","timestamp":1636064754000},"page":"3941","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Fasting-Induced Upregulation of MKP-1 Modulates the Hepatic Response to Feeding"],"prefix":"10.3390","volume":"13","author":[{"given":"Jacob","family":"Sellers","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, University of Alabama in Huntsville, Huntsville, AL 35899, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abigail","family":"Brooks","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Alabama in Huntsville, Huntsville, AL 35899, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Savanie","family":"Fernando","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Alabama in Huntsville, Huntsville, AL 35899, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabrielle","family":"Westenberger","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Alabama in Huntsville, Huntsville, AL 35899, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sadie","family":"Junkins","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Alabama in Huntsville, Huntsville, AL 35899, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shauri","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Alabama in Huntsville, Huntsville, AL 35899, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kisuk","family":"Min","sequence":"additional","affiliation":[{"name":"Department of Kinesiology, University of Texas at El Paso, El Paso, TX 79968, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9166-9548","authenticated-orcid":false,"given":"Ahmed","family":"Lawan","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Alabama in Huntsville, Huntsville, AL 35899, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1016\/j.gtc.2016.07.012","article-title":"Obesity Epidemiology Worldwide","volume":"45","author":"Mincey","year":"2016","journal-title":"Gastroenterol. 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