Common mouse models of chronic kidney disease are not associated with cachexia

常见的慢性肾病小鼠模型与恶病质无关

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作者:Benjamin Lair #, Marlène Lac #, Lucas Frassin, Manon Brunet, Marie Buléon, Guylène Feuillet, Claire Maslo, Marie Marquès, Laurent Monbrun, Virginie Bourlier, Emilie Montastier, Nathalie Viguerie, Geneviève Tavernier, Claire Laurens, Cedric Moro

Abstract

The 5/6 nephrectomy and adenine-induced nephropathy mouse models have been extensively used to study Chronic Kidney Disease (CKD)-related cachexia. One common caveat of these CKD models is the cross-sectional nature of comparisons made versus controls. We here performed a comprehensive longitudinal assessment of body composition and energy metabolism in both models. The most striking finding is that weight loss is largely driven by reduced food intake which promotes rapid loss of lean and fat mass. However, in both models, mice catch up weight and lean mass a few days after the surgery or when they are switched back to standard chow diet. Muscle force and mass are fully recovered and no sign of cachexia is observed. Our data demonstrate that the time-course of kidney failure and weight loss are unrelated in these common CKD models. These data highlight the need to reconsider the relative contribution of direct and indirect mechanisms to muscle wasting observed in CKD.

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