Diabetes (New York, N.Y.), 2020-09, Vol.69 (9), p.2003-2016
2020
Volltextzugriff (PDF)
Details
- Autor(en) / Beteiligte
- Titel
- A Small Molecule, UAB126, Reverses Diet-Induced Obesity and its Associated Metabolic Disorders
- Ist Teil von
- Diabetes (New York, N.Y.), 2020-09, Vol.69 (9), p.2003-2016
- Ort / Verlag
- United States: American Diabetes Association
- Erscheinungsjahr
- 2020
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- Targeting retinoid X receptor (RXR) has been proposed as one of the therapeutic strategies to treat individuals with metabolic syndrome, as RXR heterodimerizes with multiple nuclear receptors that regulate genes involved in metabolism. Despite numerous efforts, RXR ligands (rexinoids) have not been approved for clinical trials to treat metabolic syndrome due to the serious side effects such as hypertriglyceridemia and altered thyroid hormone axis. In this study, we demonstrate a novel rexinoid-like small molecule, UAB126, which has positive effects on metabolic syndrome without the known side effects of potent rexinoids. Oral administration of UAB126 ameliorated obesity, insulin resistance, hepatic steatosis, and hyperlipidemia without changes in food intake, physical activity, and thyroid hormone levels. RNA-sequencing analysis revealed that UAB126 regulates the expression of genes in the liver that are modulated by several nuclear receptors, including peroxisome proliferator-activated receptor α and/or liver X receptor in conjunction with RXR. Furthermore, UAB126 not only prevented but also reversed obesity-associated metabolic disorders. The results suggest that optimized modulation of RXR may be a promising strategy to treat metabolic disorders without side effects. Thus, the current study reveals that UAB126 could be an attractive therapy to treat individuals with obesity and its comorbidities.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0012-1797eISSN: 1939-327XDOI: 10.2337/db19-1001Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7458036
- Format
- –
- Schlagworte
- Animals, Clinical trials, Diet, High-Fat, Fatty liver, Fatty Liver - blood, Fatty Liver - drug therapy, Food intake, Hyperlipidemia, Hyperlipidemias - blood, Hyperlipidemias - drug therapy, Hypertriglyceridemia, Insulin, Insulin Resistance - physiology, Lipids - blood, Liver - drug effects, Liver X receptors, Male, Metabolic disorders, Metabolic syndrome, Mice, Nuclear receptors, Obesity, Obesity - blood, Obesity - drug therapy, Oral administration, Pharmacology and Therapeutics, Physical activity, Precision medicine, Retinoid X receptors, Retinoid X Receptors - agonists, Ribonucleic acid, RNA, Sequence analysis, Side effects, Steatosis, Thyroid, Thyroid gland