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This study tested CS-3150, a novel nonsteroidal, selective MR antagonist, in genetically obese db/db mice. CS-3150 (3 mg/kg/day) was given for 8 weeks, and metabolic traits, tissue morphology, inflammatory gene expression, and insulin signaling via Akt phosphorylation were analyzed. Treatment enhanced insulin sensitivity (p \u003C 0.05) and reduced adipocyte size, visceral fat, and hepatic lipid deposition (p \u003C 0.01) with lower macrophage infiltration and inflammatory markers. In vitro, CS-3150 restored insulin-induced Akt phosphorylation, unlike eplerenone, supporting therapeutic potential through attenuated adipose inflammation and improved insulin signaling.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/a-novel-mineralocorticoid-receptor-blocker-cs-3150-improves-insulin-resistance-and-reduces-inflammation-in-dbdb-mice/405659/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/a-novel-mineralocorticoid-receptor-blocker-cs-3150-improves-insulin-resistance-and-reduces-inflammation-in-dbdb-mice/405659.png","ImageObject",300,407,{"name":92,"@type":93},"Noah","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-03","2026-09-28",true,{"@type":102,"interactionType":103,"userInteractionCount":44},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What is CS-3150 and what does the study investigate?","Question",{"text":112,"@type":113},"CS-3150 is a novel nonsteroidal, selective mineralocorticoid receptor antagonist. The study evaluates its metabolic effects in obese db/db mice and its impact on insulin signaling compared with eplerenone.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How was CS-3150 administered in the in vivo experiments?",{"text":117,"@type":113},"Male db/db mice received CS-3150 at 3 mg/kg/day for 8 weeks while maintained on a normal chow diet.",{"name":119,"@type":110,"acceptedAnswer":120},"What main metabolic and molecular outcomes did CS-3150 produce?",{"text":121,"@type":113},"CS-3150 improved insulin sensitivity, reduced adipocyte size and fat accumulation, and decreased hepatic lipid deposition. It also lowered macrophage infiltration and inflammatory marker expression in white adipose tissue, alongside restored insulin signaling through Akt phosphorylation.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},405659,1790674287,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":44,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":44,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":144,"preview_page_count":4},8796095462418,"https://ap-avatar.wpscdn.com/avatar/80000253c1241d02b47?x-image-process=image/resize,m_fixed,w_180,h_180&k=1778826106357471780","Korean J Physiol Pharmacol 2026;30(1):31-39 [https://doi.org/10.4196/kjpp.25.038](https://doi.org/10.4196/kjpp.25.038)  \nOriginal Article ~~  ~~A novel mineralocorticoid receptor blocker, CS-3150, improves insulin resistance and reduces inflammation in db/db mice  \nOyunbileg Bavuu1,2, Daiju Fukuda1,2,*, Uugantsetseg Munkhjargal2, Byambasuren Ganbaatar2, Tomoya Hara2, Shusuke Yagi2, Takeshi Soeki2, and Masataka Sata2  \n1Department of Cardiovascular Medicine, Osaka Metropolitan University Graduate School of Medicine, Osaka 545-8585, Japan, 2Department of Cardiovascular Medicine, Tokushima University Graduate School of Biomedical Sciences, Tokushima 770-8503, Japan  \nARTICLE INFO  \nReceived February 1, 2025  \nRevised July 3, 2025  \nAccepted July 11, 2025  \nPublished online December 4, 2025  \n*Correspondence  \nDaiju Fukuda  \n[E-mail: daiju.fukuda@omu.ac.jp](E-mail: daiju.fukuda@omu.ac.jp)  \nKeyWords  \nCS-3150  \nInsulin resistance Mineralocorticoid receptor Obesity  \nABSTRACT Aldosterone plays a central role in regulating blood pressure and electrolyte balance, and emerging evidence implicates its involvement in metabolic disorders. This study evaluated the metabolic effects of CS-3150, a novel nonsteroidal and selective mineralocorticoid receptor (MR) antagonist, in genetically obese db/db mice. Mice were administered CS-3150 (3 mg/kg/day) for 8 weeks while maintained on a normal chow diet. Metabolic parameters, tissue morphology, inflammatory gene expression, and insulin signaling—assessed via Akt phosphorylation—were examined using standard biochemical and molecular techniques. CS-3150 treatment significantly improved insulin sensitivity (p \u003C 0.05) without notable changes in fasting blood glucose or lipid profiles. However, CS-3150 markedly reduced adipocyte size, visceral fat accumulation, and hepatic lipid deposition (p \u003C 0.01). These changes were accompanied by decreased macrophage infiltration (p \u003C 0.01) and reduced expression of inflammatory markers, including Vcam1, Sele, and Il6 in white adipose tissue (p \u003C 0.05) . In vitro, aldosterone impaired insulin-induced Akt phosphorylationin 3T3-L1 adipocytes, HepG2 hepatocytes, and C2C12 myotubes. CS-3150 treatment reversed this effect, whereas the traditional MR antagonist eplerenone failed to do so at equivalent concentrations. In conclusion, CS-3150 improved insulin sensitivity in obese diabetic mice, likely through attenuation of adipose inflammation, reduction in fat accumulation, and enhancement of insulin signaling. These findings support the potential of CS-3150 as a therapeutic agent for obesity-associated metabolic dysfunction.  \nINTRODUCTION  \nAldosterone is a key component of the renin-angiotensinaldosterone system, produced by the adrenal glands and responsible for regulating sodium and potassium balance in the human body [1]. Overactivation of the mineralocorticoid receptor (MR) and elevated aldosterone levels are implicated in the pathogenesis of cardiometabolic disorders, particularly cardiovascular disease, obesity, and diabetes [2]. However, the underlying mechanisms remain incompletely understood [3].  \nSpironolactone and eplerenone are traditional MR antagonists that effectively inhibit aldosterone’s actions. These agents have steroid-based chemical structures and play an important role in guideline-directed therapy for cardiovascular and metabolic conditions. However, their clinical use is limited to some extent due to adverse effects. Spironolactone has low specificity for MR and is associated with side effects related to the inhibition of testosterone and progesterone signaling [4]. Consequently, a nextgeneration MR antagonist, eplerenone, was developed. It offers more selective MR binding and a lower risk of gynecomastia  \nThis is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original wor","cbCaiqyIeGizLln6","https://ap.wps.com/l/cbCaiqyIeGizLln6","pdf",1205587,"English","# Introduction\n## Aldosterone and MR in metabolic disease\n## Traditional MR antagonists and limitations\n## Rationale for CS-3150\n# Methods\n## Animals and experimental design","[{\"question\":\"What is CS-3150 and what does the study investigate?\",\"answer\":\"CS-3150 is a novel nonsteroidal, selective mineralocorticoid receptor antagonist. The study evaluates its metabolic effects in obese db/db mice and its impact on insulin signaling compared with eplerenone.\"},{\"question\":\"How was CS-3150 administered in the in vivo experiments?\",\"answer\":\"Male db/db mice received CS-3150 at 3 mg/kg/day for 8 weeks while maintained on a normal chow diet.\"},{\"question\":\"What main metabolic and molecular outcomes did CS-3150 produce?\",\"answer\":\"CS-3150 improved insulin sensitivity, reduced adipocyte size and fat accumulation, and decreased hepatic lipid deposition. It also lowered macrophage infiltration and inflammatory marker expression in white adipose tissue, alongside restored insulin signaling through Akt phosphorylation.\"}]","A novel mineralocorticoid receptor blocker, CS-3150, improves insulin resistance and reduces inflammation in db/db mice | PDF",1790561310,23]