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However, the effects of CLA on inflammation and glucose metabolism are controversial. The underlying mechanisms governing the gut microbiota and sexual dimorphisms have also not been elucidated. The present study assessed the effect of CLA on glucose and lipid metabolism in established obesity and examined the mechanism of action based on gut microbiota. Four\u2010week\u2010old C57BL\/6J mice were fed a high\u2010fat diet (HFD) for 10\u00a0weeks to induce obesity. The diet\u2010induced obese (DIO) mice were fed an HFD supplemented with mixed CLA (50% cis\u20109, trans\u201011 isomer and 50% trans\u201010, cis\u201012 isomers, 0.2% wt\/wt) for 15\u00a0weeks. CLA supplementation remarkably reversed body weight in both sexes. CLA favored anti\u2010inflammatory microbiota in male mice, mediating increased short\u2010chain fatty acids and decreased lipopolysaccharide (LPS) production, which alleviated global inflammation and improved insulin sensitivity via inhibition of the TLR4\u2010NF\u2010\u03baB pathway in adipose tissue. CLA promoted the growth of hydrogen sulfide\u2010producing\n                    <jats:italic>Desulfovibrio<\/jats:italic>\n                    and the release of LPS in female mice, which aggravated adipose inflammation and insulin resistance. Although CLA impaired glucose metabolism in females, brown adipose tissue was significantly activated with browning of white adipose tissue in both sexes, which led to enhanced energy expenditure. Fecal transplantation from CLA\u2010treated mice to DIO mice mimicked the sex\u2010dependent phenotype. In conclusion, CLA decreased body weight and increased energy expenditure but sex\u2010dependently modulated insulin resistance via the gut\u2010adipose axis.\n                  <\/jats:p>","DOI":"10.1096\/fj.202002161rr","type":"journal-article","created":{"date-parts":[[2021,3,18]],"date-time":"2021-03-18T06:28:35Z","timestamp":1616048915000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Mixed conjugated linoleic acid sex\u2010dependently reverses high\u2010fat diet\u2010induced insulin resistance via the gut\u2010adipose axis"],"prefix":"10.1096","volume":"35","author":[{"given":"Haoyu","family":"Li","sequence":"first","affiliation":[{"name":"National Engineering Laboratory of Intelligent Food Technology and Equipment Zhejiang Key Laboratory for Agro\u2010Food Processing Hangzhou China"},{"name":"Fuli Institute of Food Science College of Biosystems Engineering and Food Science Zhejiang University Hangzhou 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