{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T03:42:47Z","timestamp":1790480567127,"version":"4.1.0"},"reference-count":53,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,4,16]],"date-time":"2025-04-16T00:00:00Z","timestamp":1744761600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl J Eating Disorders"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Some patients with anorexia nervosa (AN) exhibit an aversion to high\u2010fat food. The hypothalamus plays a crucial role in feeding behavior. This study investigated the role of epigenetic modifications in the hypothalamus of male rats exhibiting a weight gain resistance (WR) phenotype induced by a high\u2010fat diet (HFD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>Male Sprague\u2013Dawley (SD) rats were divided into normal diet (ND) and HFD groups for 9\u2009weeks. Rats in the HFD group were then divided into HFD\u2010induced obese (HFO) or HFD\u2010induced WR phenotype (HFWR) groups, and body weight and food intake were monitored for 24\u2009days. Samples such as hypothalamus and serum were collected.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The hypothalamus of HFWR rats showed increased 5\u2010methylcytosine (5mC) levels. Whole\u2010genome bisulfite sequencing (WGBS) analysis revealed that the level of 5mC in the hypothalamic DNA of HFWR rats was higher than that of HFO rats. The hypothalamus of HFWR rats displayed molecular disturbances in appetite systems. Through integrated analysis of the methylome and transcriptome, we discovered that alterations in methylation levels directly influenced changes in the galanin and IGF systems. Five genes (\n                      <jats:italic>Aurkb<\/jats:italic>\n                      ,\n                      <jats:italic>Cdkn1a<\/jats:italic>\n                      ,\n                      <jats:italic>Galr1<\/jats:italic>\n                      ,\n                      <jats:italic>ND2<\/jats:italic>\n                      , and\n                      <jats:italic>Tf<\/jats:italic>\n                      ) with promoter hypermethylation may be involved in appetite system disturbances. Furthermore, HFD\u2010induced alteration of 5mC affects PI3K\/Akt signaling activation, resulting in increased neuroinflammation and apoptosis in the ventromedial nucleus of the hypothalamus (VMH) in HFWR rats.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Our study suggests that 5mC\u2010mediated molecular disturbances in the hypothalamic appetite system and activation of PI3K\/Akt signaling in the VMH may serve as a potential pathogenic basis for HFWR.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/eat.24442","type":"journal-article","created":{"date-parts":[[2025,4,16]],"date-time":"2025-04-16T06:08:31Z","timestamp":1744783711000},"page":"1332-1344","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Epigenetics\u2010Driven Appetite System Disorders and\n                    <scp>PI3K<\/scp>\n                    \/\n                    <scp>AKT<\/scp>\n                    Signaling Activation Mediate a Weight Gain Resistance Phenotype Induced by a High\u2010Fat Diet in Male Rats"],"prefix":"10.1002","volume":"58","author":[{"given":"Ming\u2010Jie","family":"Li","sequence":"first","affiliation":[{"name":"Shanghai\u2010MOST Key Laboratory of Health and Disease Genomics, NHC Key Lab of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, School of Basic Medical Sciences Fudan University  Shanghai China"},{"name":"College of Food Science and Technology Shanghai Ocean University  Shanghai China"},{"name":"State Key Laboratory of Dairy Biotechnology, Shanghai Engineering Research Center of Dairy Biotechnology, Dairy Research Institute Bright Dairy &amp; Food Co. Ltd.  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao\u2010Xuan","family":"Du","sequence":"additional","affiliation":[{"name":"Shanghai\u2010MOST Key Laboratory of Health and Disease Genomics, NHC Key Lab of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, School of Basic Medical Sciences Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng\u2010Ning","family":"Lan","sequence":"additional","affiliation":[{"name":"Shanghai\u2010MOST Key Laboratory of Health and Disease Genomics, NHC Key Lab of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, School of Basic Medical Sciences Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu\u2010Yi","family":"Ye","sequence":"additional","affiliation":[{"name":"Shanghai\u2010MOST Key Laboratory of Health and Disease Genomics, NHC Key Lab of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, School of Basic Medical Sciences Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Xu","sequence":"additional","affiliation":[{"name":"Shanghai\u2010MOST Key Laboratory of Health and Disease Genomics, NHC Key Lab of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, School of Basic Medical Sciences Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Liu","sequence":"additional","affiliation":[{"name":"Shanghai\u2010MOST Key Laboratory of Health and Disease Genomics, NHC Key Lab of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, School of Basic Medical Sciences Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi\u2010Xiao","family":"Wu","sequence":"additional","affiliation":[{"name":"Shanghai\u2010MOST Key Laboratory of Health and Disease Genomics, NHC Key Lab of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, School of Basic Medical Sciences Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai\u2010Yang","family":"Xia","sequence":"additional","affiliation":[{"name":"Shanghai\u2010MOST Key Laboratory of Health and Disease Genomics, NHC Key Lab of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, School of Basic Medical Sciences Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua\u2010Yue","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shanghai\u2010MOST Key Laboratory of Health and Disease Genomics, NHC Key Lab of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, School of Basic Medical Sciences Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Guo","sequence":"additional","affiliation":[{"name":"Shanghai\u2010MOST Key Laboratory of Health and Disease Genomics, NHC Key Lab of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, School of Basic Medical Sciences Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zi\u2010Long","family":"Yang","sequence":"additional","affiliation":[{"name":"College of Food Science and Technology Shanghai Ocean University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng\u2010Jun","family":"Wu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Dairy Biotechnology, Shanghai Engineering Research Center of Dairy Biotechnology, Dairy Research Institute Bright Dairy &amp; Food Co. 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Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9242-4040","authenticated-orcid":false,"given":"Hua\u2010Jun","family":"Zheng","sequence":"additional","affiliation":[{"name":"Shanghai\u2010MOST Key Laboratory of Health and Disease Genomics, NHC Key Lab of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, School of Basic Medical Sciences Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,4,16]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1369-1600.2011.00360.x"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.irn.2017.06.006"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/eat.22374"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/pcn.12857"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1586\/17474124.2016.1166953"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0804810105"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2015.00187"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2044-8341.1974.tb02300.x"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-14-413"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/0195-6663(88)90063-3"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40519-022-01388-5"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40519-018-0567-1"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-49521-2"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2016.00256"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00096.2014"},{"key":"e_1_2_10_17_1","first-page":"1327","article-title":"Cooperation Between Galanin and Insulin in Facilitating Glucose Transporter 4 Translocation in Adipose Cells of Diabetic Rats","volume":"33","author":"Guo L. 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