{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T16:56:12Z","timestamp":1780332972385,"version":"3.54.1"},"reference-count":47,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","license":[{"start":{"date-parts":[[2020,7,28]],"date-time":"2020-07-28T00:00:00Z","timestamp":1595894400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Hepatol Commun"],"published-print":{"date-parts":[[2020,9]]},"abstract":"<jats:p>CHS\u2010131 is a selective peroxisome proliferator\u2010activated receptor gamma modulator with antidiabetic effects and less fluid retention and weight gain compared to thiazolidinediones in phase II clinical trials. We investigated the effects of CHS\u2010131 on metabolic parameters and liver histopathology in a diet\u2010induced obese (DIO) and biopsy\u2010confirmed mouse model of nonalcoholic steatohepatitis (NASH). Male C57BL\/6JRj mice were fed the amylin liver NASH diet (40% fat with trans\u2010fat, 20% fructose, and 2% cholesterol). After 36 weeks, only animals with biopsy\u2010confirmed steatosis and fibrosis were included and stratified into treatment groups (n\u00a0=\u00a012\u201013) to receive for the next 12 weeks (1) low\u2010dose CHS\u2010131 (10\u00a0mg\/kg), (2) high\u2010dose CHS\u2010131 (30\u00a0mg\/kg), or (3) vehicle. Metabolic parameters, liver pathology, metabolomics\/lipidomics, markers of liver function and liver, and subcutaneous and visceral adipose tissue gene expression profiles were assessed. CHS\u2010131 did not affect body weight, fat mass, lean mass, water mass, or food intake in DIO\u2010NASH mice with fibrosis. CHS\u2010131 improved fasting insulin levels and insulin sensitivity as assessed by the intraperitoneal insulin tolerance test. CHS\u2010131 improved total plasma cholesterol, triglycerides, alanine aminotransferase, and aspartate aminotransferase and increased plasma adiponectin levels. CHS\u2010131 (high dose) improved liver histology and markers of hepatic fibrosis. DIO\u2010NASH mice treated with CHS\u2010131 demonstrated a hepatic shift to diacylglycerols and triacylglycerols with a lower number of carbons, increased expression of genes stimulating fatty acid oxidation and browning, and decreased expression of genes promoting fatty acid synthesis, triglyceride synthesis, and inflammation in adipose tissue. <jats:italic toggle=\"yes\">Conclusion:<\/jats:italic> CHS\u2010131 improves liver histology in a DIO and biopsy\u2010confirmed mouse model of NASH by altering the hepatic lipidome, reducing insulin resistance, and improving lipid metabolism and inflammation in adipose tissue.<\/jats:p>","DOI":"10.1002\/hep4.1558","type":"journal-article","created":{"date-parts":[[2020,7,28]],"date-time":"2020-07-28T12:57:22Z","timestamp":1595941042000},"page":"1302-1315","source":"Crossref","is-referenced-by-count":18,"title":["The Selective Peroxisome Proliferator\u2010Activated Receptor Gamma Modulator CHS\u2010131 Improves Liver Histopathology and Metabolism in a Mouse Model of Obesity and Nonalcoholic Steatohepatitis"],"prefix":"10.1097","volume":"4","author":[{"given":"Nikolaos","family":"Perakakis","sequence":"first","affiliation":[{"name":"Department of Internal Medicine,Boston VA Healthcare System,Boston,MA"},{"name":"Beth Israel Deaconess Medical Center,Harvard Medical School,Boston,MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aditya","family":"Joshi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine,Boston VA Healthcare System,Boston,MA"},{"name":"Beth Israel Deaconess Medical Center,Harvard Medical School,Boston,MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natia","family":"Peradze","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine,Boston VA Healthcare System,Boston,MA"},{"name":"Beth Israel Deaconess Medical Center,Harvard Medical School,Boston,MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantinos","family":"Stefanakis","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine,Boston VA Healthcare System,Boston,MA"},{"name":"Beth Israel Deaconess Medical Center,Harvard Medical School,Boston,MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgia","family":"Li","sequence":"additional","affiliation":[{"name":"Coherus Biosciences,San Franscisco,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Feigh","sequence":"additional","affiliation":[{"name":"Gubra,H\u00f8rsholm,Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanne Skovgard","family":"Veidal","sequence":"additional","affiliation":[{"name":"Gubra,H\u00f8rsholm,Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glenn","family":"Rosen","sequence":"additional","affiliation":[{"name":"Coherus Biosciences,San 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