Endocrine Abstracts

Background: Chronic kidney disease aggravates loss of skeletal muscles mass and function, which is an independent risk factor for hospitalisation, morbidity and mortality. Glucocorticoid signalling has been implicated as a critical factor in the pathogenesis of muscle atrophy in kidney disease. This study tests whether genetic deletion of the glucocorticoid-activating enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11bHSD1) protects against muscle atrophy in the adenine-diet mouse model of renal impairment.

Methods: The experiment used 9-week-old male mice with wild-type (WT) or global 11bHSD1 knock-out (11bKO) genetic background. Persistent renal impairment was induced through dietary exposure to adenine. Animals received either normal chow or chow supplemented with 0.15% adenine for 7 weeks (n=8-11 animals per experimental group). Grip strength was measured as a readout of muscle function in vivo. Quadriceps, soleus and tibialis anterior muscles were dissected post-mortem for measurement of muscle weights.

Results: Adenine-induced renal impairment led to a significant reduction in quadriceps muscle weight in WT mice (-19.4%, P<0.001) and in 11bKO mice (-16.0%, P<0.001). The reduction in quadriceps muscle weight was not significantly different between WT and 11bKO groups. Adenine treatment also led to a comparable muscle weight reduction in WT and 11bKO mice for soleus muscle (WT: -20.2%, P<0.01; 11bKO: -19.0%, P<0.01), but not for tibialis anterior muscle (WT: -3.3%, p>0.05; 11bKO: -5.7%, p>0.05). Mean grip strength was not significantly different between adenine-treated WT and 11bKO mice (148.7g vs 133.1g, p>0.05). There was no discernible phenotype divergence with genetic deletion of 11bHSD1 in the control condition of normal chow in terms of body weight, muscle weights or grip strength.

Summary: Genetic deletion of 11bHSD1 did not reduce skeletal muscle atrophy in the adenine-diet mouse model of renal impairment. Quadriceps and soleus muscles were more susceptible to atrophy than tibialis anterior muscle in the adenine-diet mouse model of renal impairment.