Carvalho 2024 Lab Anim (NY)
| Carvalho LRRA, Shimari M, Boeder AM, Zhuge Z, Cai M, Leijding C, Gastaldello S, Kleschyov AL, Schiffer TA, Guimarães DD, Picozzi G, Lund LH, Fellström B, Weitzberg E, Lundberg JO, Hagberg CE, Pironti G, Andersson DC, Carlström M (2024) A novel model of cardiovascular-kidney-metabolic syndrome combining unilateral nephrectomy and high-salt-sugar-fat diet in mice. Lab Anim (NY) 53:336-46. https://doi.org/10.1038/s41684-024-01457-5 |
Carvalho Lucas Rannier RA, Shimari Miho, Boeder Ariela Maina, Zhuge Zhengbing, Cai Min, Leijding Cecilia, Gastaldello Stefano, Kleschyov Andrei L, Schiffer Tomas A, Guimaraes Drielle Dantas, Picozzi Gaia, Lund Lars H, Fellstroem Bengt, Weitzberg Eddie, Lundberg Jon O, Hagberg Carolina E, Pironti Gianluigi, Andersson Daniel C, Carlstroem Mattias (2024) Lab Anim (NY)
Abstract: The aim of this study was to explore biological interaction and pathophysiology mechanisms in a new mouse model of cardiovascular-kidney-metabolic (CKM) syndrome, induced by chronic moderate renal failure in combination with consumption of a customized Western diet rich in carbohydrates, fat and salt. Male C57BL/6J mice were subjected to unilateral nephrectomy, fed a customized Western diet rich not only in sugar and fat but also in salt, and followed for 12 weeks or 20 weeks. Sham-operated mice on a standard chow served as healthy controls. Body composition, weight gain, glucose metabolism, fat distribution, blood pressure, cardiac function, vascular reactivity, renal function, inflammation and mitochondrial function were measured and combined with biochemical and histopathological analyses. The novel triple-hit model of CKM syndrome showed signs and symptoms of metabolic syndrome, disturbed glucose metabolism, impaired adipocyte physiology and fat redistribution, cardiovascular dysfunction, renal damage and dysfunction, systemic inflammation, elevated blood pressure and cardiac remodeling. The pathological changes were more pronounced in mice after prolonged exposure for 20 weeks, but no deaths occurred. In the present mouse model of CKM syndrome, profound and significant metabolic, cardiac, vascular and renal dysfunctions and injuries emerged by using a Western diet rich not only in fat and carbohydrates but also in salt. This multisystem disease model could be used for mechanistic studies and the evaluation of new therapeutic strategies.
• Bioblast editor: Plangger M • O2k-Network Lab: SE Stockholm Weitzberg E
Labels: MiParea: Respiration
Pathology: Cardiovascular, Other
Organism: Mouse Tissue;cell: Heart, Kidney Preparation: Isolated mitochondria
Coupling state: LEAK, OXPHOS
Pathway: N, S, CIV, NS, ROX
HRR: Oxygraph-2k, O2k-Fluorometer
2024-10, AmR
