Dapagliflozin regulates autophagy in nephropathy associated with non-diabetic obesity via elevated plasma β-hydroxybutyrate levels
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Le résumé fourni par la source
Obesity is a major contributor to chronic kidney disease, accounting for approximately 20%-25% of cases globally. In obesity-related kidney disease (OKD), ectopic lipid accumulation in renal proximal tubule cells impairs autophagic flux, exacerbating kidney injury. Sodium-glucose cotransporter-2 (SGLT-2) inhibitors, such as dapagliflozin, induce a fasting-like metabolic state and increase circulating β-hydroxybutyrate (β-HB) levels. However, the role of β-HB in modulating autophagic flux in OKD remains unclear. To investigate the potential involvement of β-HB in the renoprotective effects of dapagliflozin, diet-induced obesity (DIO) mice were used. Twelve DIO mice maintained on a high-fat diet (HFD) were randomly assigned to receive dapagliflozin or the β-HB precursor 1,3-butanediol (n = 6 per group). For each treatment, six DIO mice on HFD served as experimental models and were compared with six age-matched mice fed a standard chow diet as controls. Our study showed that dapagliflozin treatment significantly increased plasma β-HB levels and improved metabolic profiles in DIO mice. Exogenous ketone supplementation elicited similar metabolic and renoprotective effects. Both interventions enhanced autophagic flux in proximal tubule cells and attenuated structural damage in glomeruli and tubules. The renoprotective effects of dapagliflozin were associated with improved autophagic flux, suggesting that elevated β-HB levels may contribute to these benefits. The data suggest that dapagliflozin improves autophagic flux in OKD, potentially mediated by increased plasma β-HB levels. These findings provide insight into the metabolic mechanisms underlying SGLT-2 inhibitor-mediated renoprotection and highlight β-HB as a possible therapeutic target in OKD.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Dapagliflozin regulates autophagy in nephropathy associated with non-diabetic obesity via elevated plasma β-hydroxybutyrate levels
- Date Crossref
- 24/03/2026
- Éditeur
- Portland Press Ltd.
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Tianjin Infectious Diseases Hospital pays non établi dans la noticeÉtablissement de santé
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Tianjin Medical University Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology pays non établi dans la noticeUniversité ou école supérieure
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Beijing Luhe Hospital Affiliated to Capital Medical University Beijing Luhe Hospital pays non établi dans la noticeÉtablissement de santé
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Xinjiang Medical University pays non établi dans la noticeUniversité ou école supérieure
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Sixth Affiliated Hospital of Xinjiang Medical University pays non établi dans la noticeÉtablissement de santé
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Jinjiang 362200 pays non établi dans la noticeInstitution
Tianjin Infectious Diseases Hospital, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology — Tianjin Medical University et Beijing Luhe Hospital — Beijing Luhe Hospital Affiliated to Capital Medical University, avec 3 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.