{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T03:10:41Z","timestamp":1789960241509,"version":"4.0.1"},"reference-count":60,"publisher":"The Endocrine Society","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Obesity arises from impaired energy balance, which is centrally coordinated by leptin through activation of the long form of leptin receptor (Leprb). Obesity causes central leptin resistance. However, whether enhanced peripheral leptin sensitivity could overcome central leptin resistance remains obscure. A peripheral metabolic organ targeted by leptin is the liver, with low Leprb expression. We here show that mice fed a high-fat diet (HFD) and obese patients with hepatosteatosis exhibit increased expression of hepatic helicase with zinc finger 2, a transcriptional coactivator (Helz2), which functions as a transcriptional coregulator of several nuclear receptors, including peroxisome proliferator-activated receptor \u03b3 in vitro. To explore the physiological importance of Helz2, we generated Helz2-deficient mice and analyzed their metabolic phenotypes. Helz2-deficient mice showing hyperleptinemia associated with central leptin resistance were protected against HFD-induced obesity and had significantly up-regulated hepatic Leprb expression. Helz2 deficiency and adenovirus-mediated liver-specific exogenous Leprb overexpression in wild-type mice significantly stimulated hepatic AMP-activated protein kinase on HFD, whereas Helz2-deficient db\/db mice lacking functional Leprb did not. Fatty acid-\u03b2 oxidation was increased in Helz2-deficeint hepatocytes, and Helz2-deficient mice revealed increased oxygen consumption and decreased respiratory quotient in calorimetry analyses. The enhanced hepatic AMP-activated protein kinase energy-sensing pathway in Helz2-deficient mice ameliorated hyperlipidemia, hepatosteatosis, and insulin resistance by reducing lipogenic gene expression and stimulating lipid-burning gene expression in the liver. These findings together demonstrate that Helz2 deficiency ameliorates HFD-induced metabolic abnormalities by stimulating endogenous hepatic Leprb expression, despite central leptin resistance. Hepatic HELZ2 might be a novel target molecule for the treatment of obesity with hepatosteatosis.<\/jats:p>","DOI":"10.1210\/en.2013-2160","type":"journal-article","created":{"date-parts":[[2014,7,8]],"date-time":"2014-07-08T17:30:38Z","timestamp":1404840638000},"page":"3459-3472","source":"Crossref","is-referenced-by-count":20,"title":["Protection Against High-Fat Diet-Induced Obesity in Helz2-Deficient Male Mice Due to Enhanced Expression of Hepatic Leptin Receptor"],"prefix":"10.1210","volume":"155","author":[{"given":"Satoshi","family":"Yoshino","sequence":"first","affiliation":[{"name":"Departments of Medicine and Molecular Science (S.Y., T.Sat., M.Y., K.H., T.To., A.K.-T., S.K., S.O., H.S., A.O., T.Tu., Ma.Mori) Gunma University Graduate School of Medicine, Maebashi, 371-8511 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsurou","family":"Satoh","sequence":"first","affiliation":[{"name":"Departments of Medicine and Molecular Science (S.Y., T.Sat., M.Y., 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Fatty liver disease and fatty acid oxidation","volume":"290","author":"Reddy","year":"2006","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"2020071612212547000_B43","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.1002\/hep.24155","article-title":"Transcription coactivator mediator subunit MED1 is required for the development of fatty liver in the mouse","volume":"53","author":"Bai","year":"2011","journal-title":"Hepatology"},{"key":"2020071612212547000_B44","doi-asserted-by":"crossref","first-page":"1508","DOI":"10.1210\/en.2005-1132","article-title":"Peroxisome proliferator-activated receptor \u03b1 mediates the effects of high-fat diet on hepatic gene expression","volume":"147","author":"Patsouris","year":"2006","journal-title":"Endocrinology"},{"key":"2020071612212547000_B45","doi-asserted-by":"crossref","first-page":"1076","DOI":"10.1016\/j.bbalip.2009.06.005","article-title":"A pan-PPAR ligand induces hepatic fatty acid oxidation in PPAR\u03b1-\/- mice possibly through PGC-1 mediated PPAR\u03b4 coactivation","volume":"1791","author":"R\u00f8st","year":"2009","journal-title":"Biochim Biophys Acta"},{"key":"2020071612212547000_B46","doi-asserted-by":"crossref","first-page":"4317","DOI":"10.1128\/MCB.02222-06","article-title":"Leptin stimulates fatty acid oxidation and peroxisome proliferator-activated receptor \u03b1 gene expression in mouse C2C12 myoblasts by changing the subcellular localization of the \u03b12 form of AMP-activated protein kinase","volume":"27","author":"Suzuki","year":"2007","journal-title":"Mol Cell Biol"},{"key":"2020071612212547000_B47","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.pone.0003614","article-title":"AMP-activated protein kinase-regulated activation of the PGC-1\u03b1 promoter in skeletal muscle cells","volume":"3","author":"Irrcher","year":"2008","journal-title":"PLoS One"},{"key":"2020071612212547000_B48","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/j.cell.2008.06.051","article-title":"AMPK and PPAR-\u03b4 agonists are exercise mimetics","volume":"134","author":"Narkar","year":"1008","journal-title":"Cell"},{"key":"2020071612212547000_B49","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1210\/er.2012-1009","article-title":"Diabetes and nonalcoholic fatty liver disease: a pathogenic duo","volume":"34","author":"Williams","year":"2013","journal-title":"Endocrine Rev"},{"key":"2020071612212547000_B50","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.2337\/db08-1571","article-title":"Sensitivity of lipid metabolism and insulin signaling to genetic alterations in hepatic peroxisome proliferator-activated receptor-\u03b3 coactivator-1\u03b1 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