Mammalian target of rapamycin inhibition impacts energy homeostasis and induces sex‐specific body weight loss in humans

Autor: Marwan Mannaa, Pia Pfennigwerth, Jens Fielitz, Maik Gollasch, Michael Boschmann
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Journal of Cachexia, Sarcopenia and Muscle, Vol 14, Iss 6, Pp 2757-2767 (2023)
Druh dokumentu: article
ISSN: 2190-6009
2190-5991
DOI: 10.1002/jcsm.13352
Popis: Abstract Background Previous data from a 2‐year randomized controlled trial (CRAD001ADE12) indicated that mammalian target of rapamycin (mTOR) inhibition by everolimus slowed cyst growth in patients with autosomal‐dominant polycystic kidney disease (ADPKD). During the trial, we noted body weight loss in some patients, particularly in women. We hypothesized that everolimus causes body weight reduction by reduced food intake and/or metabolic changes, which could lead to cachexia. Methods Within a sub‐analysis of the CRAD001ADE12 trial, body weight course was investigated regarding sex‐specific differences in 433 adult ADPKD patients (everolimus, n = 215; placebo, n = 218). One hundred four out of 111 patients who participated in the clinical trial centre in Berlin were evaluated under everolimus/placebo therapy (on drug: everolimus, n = 48; placebo, n = 56) and after therapy (off drug: everolimus, n = 15; placebo, n = 18). Eating habits and nutrient/caloric intake were evaluated by validated questionnaires. Systemic and local metabolism was evaluated in four patients after an oral glucose load (OGL) by using calorimetry and adipose/muscle tissue microdialysis. Results Within the 2‐year CRAD001ADE12 trial, a significant body weight loss was observed in female patients on everolimus versus placebo (P = 0.0029). Data of the Berlin Cohort revealed that weight loss was greater in women on everolimus versus men (P
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