Creatinine promotes adipose tissue wasting in chronic kidney disease via creatine and futile creatine cycle.

ABSTRACT:

Objective

Cachexia in chronic kidney disease (CKD) is a wasting syndrome. The futile creatine cycle (FCC) contributes to energy waste in adipocytes. Creatinine is metabolite of creatine. Whether creatinine involves in adipose wasting in CKD remains elusive.

Methods

Cachexia were assessed in unilateral ureteral obstruction induced CKD mice model. Cellular oxygen consumption and FCC-related genes expression were analyzed in adipocytes treated with creatinine in the presence of FCC inhibitor (SBI-425, inhibitor of TNAP) or creatine disruption (β-GPA, a creatine analogue that inhibits creatine transport into cells). The fate of labeled deuterated creatinine (D-3 creatinine) were traced by mass spectrometer. To determine creatinine drives adipose tissue wasting in vivo, two mice

SUBMITTER: Fang J 

PROVIDER: S-EPMC12269410 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature