{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T06:31:44Z","timestamp":1776148304056,"version":"3.50.1"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2020,11,1]],"date-time":"2020-11-01T00:00:00Z","timestamp":1604188800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81803341"],"award-info":[{"award-number":["81803341"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province, China","doi-asserted-by":"publisher","award":["2018A030313445"],"award-info":[{"award-number":["2018A030313445"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021171","name":"Guangdong Basic and Applied Basic Research Foundation","doi-asserted-by":"crossref","award":["2019A1515011036"],"award-info":[{"award-number":["2019A1515011036"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Key Field R&D Plan Project of Guangdong Province","award":["2019B020201002"],"award-info":[{"award-number":["2019B020201002"]}]},{"name":"the Innovative strong school project of Guangdong Pharmaceutical University","award":["2018KTSCX111"],"award-info":[{"award-number":["2018KTSCX111"]}]},{"name":"the projects of Guangzhou key laboratory of construction and application of new drug screening model systems","award":["201805010006"],"award-info":[{"award-number":["201805010006"]}]},{"name":"Key Laboratory of New Drug Discovery and Evaluation of ordinary universities of Guangdong province","award":["2017KSYS002"],"award-info":[{"award-number":["2017KSYS002"]}]},{"name":"the Innovation Team Projects in Universities of Guangdong Province","award":["2018KCXTD016"],"award-info":[{"award-number":["2018KCXTD016"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>Nonalcoholic fatty liver (NAFLD), a chronic progressive liver disease, is highly correlated with pathoglycemia, dyslipidemia and oxidative stress. The free fatty acid receptor 1 (FFA1) agonists have been reported to improve liver steatosis and fibrosis, and the peroxisome proliferator-activated receptor \u03b4 (PPAR\u03b4) plays a synergistic role with FFA1 in energy metabolism and fibrosis. HWL-088, a PPAR\u03b4\/FFA1 dual agonist, exerts better glucose-lowering effects than the representative FFA1 agonist TAK-875. However, the ability of HWL-088 to protect NAFLD was unknown. This study aimed to discover a new strategy for the treatment of NAFLD.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>The methionine- and choline-deficient diet (MCD)-induced Nonalcoholic steatohepatitis (NASH) model was constructed to evaluate the effects of HWL-088.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Key findings<\/jats:title>\n                  <jats:p>Administration of HWL-088 exerted multiple benefits on glucose control, lipid metabolism and fatty liver. Further mechanism research indicated that HWL-088 promotes lipid metabolism by decreasing lipogenesis and increasing lipolysis. Moreover, HWL-088 attenuates NASH by regulating the expression levels of genes related to inflammation, fibrosis and oxidative stress.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>These positive results indicated that PPAR\u03b4\/FFA1 dual agonist HWL-088 might be a potential candidate to improve multiple pathogenesis of NASH.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1111\/jphp.13342","type":"journal-article","created":{"date-parts":[[2020,7,31]],"date-time":"2020-07-31T07:59:29Z","timestamp":1596182369000},"page":"1564-1573","source":"Crossref","is-referenced-by-count":9,"title":["HWL-088, a new and highly effective FFA1\/PPAR\u03b4 dual agonist, attenuates nonalcoholic steatohepatitis by regulating lipid metabolism, inflammation and fibrosis"],"prefix":"10.1093","volume":"72","author":[{"given":"Lijun","family":"Hu","sequence":"first","affiliation":[{"name":"School of Pharmacy, Guangdong Pharmaceutical University , Guangzhou,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zongtao","family":"Zhou","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Guangdong Pharmaceutical University , Guangzhou,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liming","family":"Deng","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Guangdong Pharmaceutical University , Guangzhou,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiang","family":"Ren","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Guangdong Pharmaceutical University , Guangzhou,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zongyu","family":"Cai","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Guangdong Pharmaceutical University , 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