Leon, Stephane and Benoit, Julie and Clark, Samantha and Zizzari, Philippe and Yang, Bin and Dugail, Isabelle and Merabtene, Fatiha and Clement, Karine and Eygret, Louise and Dupuy, Nathalie and Delpech, Jean-Christophe and Rossitto, Moira and Mack, Matthias and Leste-Lasserre, Thierry and Finan, Brian and Cota, Daniela and Quarta, Carmelo (2025) GLP-1-Mediated Targeting of Inflammation Corrects Obesogenic Memory in Male Mice. DIABETES, 74 (9). pp. 1525-1534. ISSN 0012-1797, 1939-327X
Full text not available from this repository. (Request a copy)Abstract
Obesity-induced biologic changes often persist after weight loss and are difficult to reverse, a phenomenon known as obesogenic memory. This enduring effect is associated with metabolic inflammation, particularly in adipose tissue. In this study, we characterized a mouse model of obesogenic memory and evaluated the efficacy of the unimolecular conjugate glucagon-like peptide 1 (GLP-1)/dexamethasone (GLP-1/Dexa), which selectively and safely delivers the anti-inflammatory drug dexamethasone to GLP-1 receptor (GLP-1R)-expressing cells. We report that this precision pharmacologic approach outperformed treatment with GLP-1 or dexamethasone alone, significantly reducing body weight, food intake, adiposity, and markers of adipose tissue inflammation in male mice with obesogenic memory. In addition, we identified the CCR2/CCL2 inflammatory pathway as an important mediator of glucose intolerance and adipose tissue inflammation associated with obesogenic memory. Our findings suggest that targeting inflammation via GLP-1R signaling may be a promising therapeutic strategy to alleviate obesogenic memory and improve the long-term clinical management of metabolic diseases.ARTICLE HIGHLIGHTS Weight loss defense mechanisms and inflammation challenge metabolic disease management, with few treatments available. We developed a mouse model of obesogenic memory and investigated the efficacy of a glucagon-like peptide 1/dexamethasone (GLP-1/Dexa) conjugate that safely and cell-selectively targets inflammation in GLP-1 receptor cells. GLP-1/Dexa offers a promising strategy to correct obesogenic memory and adipose tissue inflammation in male mice. CCR2 monocytes contribute to glucose intolerance associated with obesogenic memory and may be targeted by GLP-1/Dexa.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | INSULIN-RESISTANCE; ADIPOSE-TISSUE; OBESITY; DYSFUNCTION; INCREASES; PROTECTS; REVERSES; CCR2; DIET; CB1; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Abteilung für Nephrologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 28 Jul 2026 12:26 |
| Last Modified: | 28 Jul 2026 12:26 |
| URI: | https://pred.uni-regensburg.de/id/eprint/67259 |
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