{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T17:23:00Z","timestamp":1789665780653,"version":"4.0.1"},"reference-count":49,"publisher":"Bioscientifica","issue":"3","content-domain":{"domain":["jme.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2017,4]]},"abstract":"<jats:p>Liver X receptors (LXR) are deemed as potential drug targets for atherosclerosis, whereas a role in adipose tissue expansion and its relation to insulin sensitivity remains unclear. To assess the metabolic effects of LXR activation by the dual LXR\u03b1\/\u03b2 agonist T0901317, C57BL\/6 mice fed a high-fat diet (HFD) were treated with T0901317 (30\u2009mg\/kg once daily by intraperitoneal injection) for 3 weeks. Differentiated 3T3-L1 adipocytes were used for analysing the effect of T0901317 on glucose uptake. The following results were obtained from this study. T0901317 reduced fat mass, accompanied by a massive fatty liver and lower serum adipokine levels in HFD mice. Increased adipocyte apoptosis was found in epididymal fat of T0901317-treated HFD mice. In addition, T0901317 treatment promoted basal lipolysis, but blunted the anti-lipolytic action of insulin. Furthermore, LXR activation antagonised PPAR\u03b3 target genes in epididymal fat and PPAR\u03b3-PPRE-binding activity in 3T3-L1 adipocytes. Although the glucose tolerance was comparable to that in HFD mice, the insulin response during IPGTT was significantly higher and the insulin tolerance was significantly impaired in T0901317-treated HFD mice, indicating decreased insulin sensitivity by T0901317 administration, and which was further supported by impaired insulin signalling found in epididymal fat and decreased insulin-induced glucose uptake in 3T3-L1 adipocytes by T0901317 administration. In conclusion, these findings reveal that LXR activation impairs adipose expansion by increasing adipocyte apoptosis, lipolysis and antagonising PPAR\u03b3-mediated transcriptional activity, which contributes to decreased insulin sensitivity in whole body. The potential of LXR activation being a therapeutic target for atherosclerosis might be limited by the possibility of exacerbating insulin resistance.<\/jats:p>","DOI":"10.1530\/jme-16-0196","type":"journal-article","created":{"date-parts":[[2017,3,3]],"date-time":"2017-03-03T20:10:21Z","timestamp":1488571821000},"page":"141-154","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-6","source":"Crossref","is-referenced-by-count":11,"title":["Impaired adipose expansion caused by liver X receptor activation is associated with insulin resistance in mice fed a high-fat diet"],"prefix":"10.1530","volume":"58","author":[{"given":"Yueting","family":"Dong","sequence":"first","affiliation":[{"name":"1Department of EndocrinologySir Run Run Shaw Hospital Affiliated with School of Zhejiang University, Hangzhou, Zhejiang, People\u2019s Republic of 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