{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T23:29:58Z","timestamp":1790206198327,"version":"4.1.0"},"reference-count":53,"publisher":"Portland Press Ltd.","issue":"12","license":[{"start":{"date-parts":[[2020,6,18]],"date-time":"2020-06-18T00:00:00Z","timestamp":1592438400000},"content-version":"vor","delay-in-days":17,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,6,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Hyperuricaemia (HUA) significantly increases the risk of metabolic syndrome and is strongly associated with the increased prevalence of high serum free fatty acids (FFAs) and insulin resistance. However, the underlying mechanisms are not well established, especially the effect of uric acid (UA) on adipose tissue, a vital organ in regulating whole-body energy and FFA homeostasis. In the present study, we noticed that adipocytes from the white adipose tissue of patients with HUA were hypertrophied and had decreased UCP1 expression. To test the effects of UA on adipose tissue, we built both in vitro and in vivo HUA models and elucidated that a high level of UA could induce hypertrophy of adipocytes, inhibit their hyperplasia and reduce their beige-like characteristics. According to mRNA-sequencing analysis, UA significantly decreased the expression of leptin in adipocytes, which was closely related to fatty acid metabolism and the AMPK signalling pathway, as indicated by KEGG pathway analysis. Moreover, lowering UA using benzbromarone (a uricosuric agent) or metformin-induced activation of AMPK expression significantly attenuated UA-induced FFA metabolism impairment and adipose beiging suppression, which subsequently alleviated serum FFA elevation and insulin resistance in HUA mice. Taken together, these observations confirm that UA is involved in the aetiology of metabolic abnormalities in adipose tissue by regulating leptin-AMPK pathway, and metformin could lessen HUA-induced serum FFA elevation and insulin resistance by improving adipose tissue function via AMPK activation. Therefore, metformin could represent a novel treatment strategy for HUA-related metabolic disorders.<\/jats:p>","DOI":"10.1042\/cs20200580","type":"journal-article","created":{"date-parts":[[2020,6,18]],"date-time":"2020-06-18T10:49:01Z","timestamp":1592477341000},"page":"1537-1553","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Metformin alleviates hyperuricaemia-induced serum FFA elevation and insulin resistance by inhibiting adipocyte hypertrophy and reversing suppressed white adipose tissue beiging"],"prefix":"10.1042","volume":"134","author":[{"given":"Mengqi","family":"Su","sequence":"first","affiliation":[{"name":"Department of Cardiology, The First Affiliated Hospital, Harbin Medical University, Harbin 150001, Heilongjiang Province, P. R. 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linqun","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The First Affiliated Hospital, Harbin Medical University, Harbin 150001, Heilongjiang Province, P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuangli","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The First Affiliated Hospital, Harbin Medical University, Harbin 150001, Heilongjiang Province, P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenguang","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The First Affiliated Hospital, Harbin Medical University, Harbin 150001, Heilongjiang Province, P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenyang","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The First Affiliated Hospital, Harbin Medical University, Harbin 150001, Heilongjiang Province, P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenwei","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, The State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Harbin Medical University, Harbin, 150081, Heilongjiang Province, P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7727-905X","authenticated-orcid":false,"given":"Yue","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The First Affiliated Hospital, Harbin Medical University, Harbin 150001, Heilongjiang Province, P. R. 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