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Cystathionine \u03b3\u2010lyase (CSE; also cystathionase), a principal hydrogen sulfide (H\n                    <jats:sub>2<\/jats:sub>\n                    S)\u2010synthesizing enzyme in the liver, is involved in glucose and lipid metabolism disorders. However, the roles and precise mechanisms of CSE\/H\n                    <jats:sub>2<\/jats:sub>\n                    S in obesity and its related insulin resistance remain obscure. Here we show that CSE knockout exacerbated high\u2010fat diet\u2014induced mouse obesity as well as its related insulin resistance. Further study elucidated that the inhibition of insulin and AMPK signaling pathways by CSE deficiency resulted in nuclear accumulation of Forkhead box protein O1 and subsequently promoted hepatic gluconeogenesis. These phenomena can be reversed by NaHS supplementation. However, in wild\u2010type mice, NaHS treatment ameliorates high fat diet\u2014induced obesity and metabolism disorders, indicating that maintaining an appropriate level of H\n                    <jats:sub>2<\/jats:sub>\n                    S is critical for its mutual change of positive and negative effects of obesity\u2010associated insulin resistance. Our study reveals a double\u2010edged sword effect and a novel mechanism for CSE\/H\n                    <jats:sub>2<\/jats:sub>\n                    S in obesity associated with insulin resistance and provides evidence for CSE\/H\n                    <jats:sub>2<\/jats:sub>\n                    S as a promising therapeutic potential target for obesity\u2010related insulin resistance.\u2014Guo, W., Li, D., You, Y., Li, W., Hu, B., Zhang, S., Miao, L., Xian, M., Zhu, Y., Shen, X. Cystathionine \u03b3\u2010lyase deficiency aggravates obesity\u2010related insulin resistance\n                    <jats:italic>via<\/jats:italic>\n                    FoxO1\u2010dependent hepatic gluconeogenesis. FASEB J. 33, 4212\u20134224 (2019).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201801894r","type":"journal-article","created":{"date-parts":[[2018,12,10]],"date-time":"2018-12-10T15:27:55Z","timestamp":1544455675000},"page":"4212-4224","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Cystathionine \u03b3\u2010lyase deficiency aggravates obesity\u2010related insulin resistance\n                    <i>via<\/i>\n                    FoxO1\u2010dependent hepatic gluconeogenesis"],"prefix":"10.1096","volume":"33","author":[{"given":"Wei","family":"Guo","sequence":"first","affiliation":[{"name":"Department of Pharmacology School of Pharmacy Fudan University  Shanghai 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