{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T01:45:14Z","timestamp":1791769514243,"version":"4.3.4"},"reference-count":64,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T00:00:00Z","timestamp":1791676800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T00:00:00Z","timestamp":1791676800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2021YFC2101001"],"award-info":[{"award-number":["2021YFC2101001"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Phytotherapy Research"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Obesity is a chronic, recurrent, and progressive disease caused by energy imbalance. N\n                    <jats:sup>6<\/jats:sup>\n                    \u2010methyladenosine (m\n                    <jats:sup>6<\/jats:sup>\n                    A) modification regulates fat thermogenesis, potentially counteracting obesity. Mogroside V (MV) is a triterpene glycoside extracted from\n                    <jats:italic>Siraitia grosvenorii<\/jats:italic>\n                    and has shown beneficial effects in models of obesity. However, its underlying mechanism remains unknown. The objective of this study is to investigate the effects of MV on adipose thermogenesis and explore the mechanism of m\n                    <jats:sup>6<\/jats:sup>\n                    A modifications in mediating these effects. Mitochondrial respiration analysis, histological and molecular biological methods were used to investigate the thermogenesis in differentiated C3H10T1\/2 brown adipocytes and adipose tissue in high\u2010fat diet (HFD)\u2010fed mouse models, respectively. Stable cell models with overexpression or knockdown of fat mass and obesity\u2010associated protein (FTO) were generated to investigate the effects of FTO on m\n                    <jats:sup>6<\/jats:sup>\n                    A modification and thermogenesis in brown adipocytes. Methylated RNA immunoprecipitation\u2010quantitative\u2010PCR (MeRIP\u2010qPCR) and RIP\u2010qPCR analysis were used to reveal the potential downstream molecular targets of FTO. MV improved HFD\u2010induced obesity and metabolic dysfunction in mice. MV also increased uncoupling protein 1 (UCP1) expression in brown adipose tissue and enhanced mitochondrial respiration and expression of peroxisome proliferator activated receptor \u03b3 coactivator 1\u03b1 (PGC1\u03b1) and UCP1 in differentiated C3H10T1\/2 cells. Further analysis of the relevant molecular mechanisms showed that MV suppressed FTO expression, thereby increasing m\n                    <jats:sup>6<\/jats:sup>\n                    A modification of LETM1 domain\u2010containing protein 1 (\n                    <jats:italic>Letmd1<\/jats:italic>\n                    ) mRNA. The m\n                    <jats:sup>6<\/jats:sup>\n                    A\u2010modified\n                    <jats:italic>Letmd1<\/jats:italic>\n                    transcript was recognized by the m\n                    <jats:sup>6<\/jats:sup>\n                    A reader YTH domain\u2010containing protein 2 (YTHDC2), thereby increasing the stability of\n                    <jats:italic>Letmd1<\/jats:italic>\n                    mRNA. The increased\n                    <jats:italic>Letmd1<\/jats:italic>\n                    mRNA levels were correlated with increased LETMD1 protein abundance, which subsequently enhanced the expression of PGC1\u03b1 and UCP1, ultimately promoting brown adipocyte thermogenesis. MV promoted brown adipocyte thermogenesis through the FTO\u2010m\n                    <jats:sup>6<\/jats:sup>\n                    A\u2010LETMD1\u2010UCP1 axis, suggesting a potential therapeutic strategy for obesity.\n                  <\/jats:p>","DOI":"10.1002\/ptr.70480","type":"journal-article","created":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T01:12:27Z","timestamp":1791767547000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mogroside V Promotes Brown Adipose Thermogenesis via\n                    <scp>FTO<\/scp>\n                    \u2010m\n                    <sup>6<\/sup>\n                    <scp>A<\/scp>\n                    \u2010\n                    <scp>LETMD<\/scp>\n                    1\u2010\n                    <scp>UCP<\/scp>\n                    1 Pathway to Combat Obesity"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-2871-7993","authenticated-orcid":false,"given":"Yuan\u2010hai","family":"Sun","sequence":"first","affiliation":[{"name":"Institute of Pharmacology Zhejiang University of Technology  Hangzhou People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling\u2010huan","family":"Li","sequence":"additional","affiliation":[{"name":"College of Chemistry and Materials Science Zhejiang Normal University  Jinhua People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya\u2010qian","family":"Feng","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology Zhejiang University of Technology  Hangzhou People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teng\u2010jiao","family":"Zhao","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology Zhejiang University of Technology  Hangzhou People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3203-4080","authenticated-orcid":false,"given":"Min\u2010you","family":"Qi","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology Zhejiang University of Technology  Hangzhou People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3873-4061","authenticated-orcid":false,"given":"Han\u2010bing","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology Zhejiang University of Technology  Hangzhou People's Republic of China"},{"name":"Zhejiang Key Laboratory of Green Manufacturing Technology for Chemical Drugs  Hangzhou People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,11]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.foodchem.2013.03.085"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2021.02.007"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943\u2010020\u201001220\u20107"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2010.01.003"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.110104"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202301855"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.71.10.3971"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573\u2010025\u201001183\u20108"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.2337\/db19\u20101153"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2022.105292"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature07848"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2009.05.003"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.D023788"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580\u2010018\u20100093\u2010z"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2024.1438515"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/imm.13574"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2021.101202"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010023\u201041849\u20108"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2023.113585"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.687"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnutbio.2016.12.018"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2019.104393"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2021.101358"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/7826874"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202300436"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13238\u2010020\u201000770\u20102"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010019\u201013317\u20109"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2023.106933"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.07.048"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/obr.12520"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.4103\/0976\u20100105.177703"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010023\u201039106\u2010z"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.109742"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2018.06.018"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2014.3"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2021.101173"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202100597R"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2019.1586246"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biochi.2022.07.002"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41556\u2010021\u201000835\u20102"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1111\/obr.70029"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00225.2023"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2021110439"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2016.05.041"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41418\u2010024\u201001397\u20100"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010020\u201015488\u20102"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.15252\/embr.202052348"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.2337\/db22\u20100775"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010023\u201037100\u2010z"},{"key":"e_1_2_12_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhazmat.2024.135004"},{"key":"e_1_2_12_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010022\u201035219\u2010z"},{"key":"e_1_2_12_53_1","doi-asserted-by":"publisher","DOI":"10.1002\/mnfr.201700261"},{"key":"e_1_2_12_54_1","doi-asserted-by":"publisher","DOI":"10.2903\/j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