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Am J Physiol Renal Physiol. 2019 Aug 14. doi: 10.1152/ajprenal.00203.2019. [Epub ahead of print]

Obesity Causes Renal Mitochondrial Dysfunction and Energy Imbalance and Accelerates Chronic Kidney Disease in Mice.

Author information

1
Medicine, University of Colorado Denver.
2
Renal Medicine, Univ Colorado, Denver, United States.
3
Division of Renal Diseases and Hypertension, University of Colorado Denver, United States.
4
University of Colorado Anschutz Medical Campus, Aurora, CO; Department of Pathology, United States.
5
Renal Division, University of Colorado, United States.
6
Renal, University of Colorado, United States.
7
Medicine, University of Colorado Denver, United States.
8
Medicine-Renal division, University of Colorado, United States.
9
Medicine/Nephrology, University of Colorado, Denver, United States.

Abstract

Obesity, as well as the metabolic syndrome, are well known risk factors for chronic kidney disease (CKD), but less is known about the mechanism(s) by which metabolic syndrome might accelerate kidney disease. We hypothesized that metabolic syndrome should accelerate the development of kidney disease and that it might be associated with alterations in energy metabolism.We studied the pound mouse (which develops early metabolic syndrome due to a leptin receptor deletion) and wild type littermates and compared the level of renal injury and muscle wasting following equivalent injury with oral adenine. Renal function, histology, and biochemical analyses were performed.The presence of metabolic syndrome was associated with earlier development of renal disease (12 months) and earlier mortality in pound mice compared to controls. Following administration of adenine, kidney disease was worse in pound mice and this was associated with greater tubular injury with a decrease in kidney mitochondria, lower tissue ATP levels, and worse oxidative stress. Pound mice with similar levels of renal function as adenine-treated wild type mice also showed worse sarcopenia, with lower tissue ATP and intracellular phosphate levels.In summary, our data demonstrate that Obesity and metabolic syndrome accelerate the progression of chronic kidney disease and worsen CKD-dependent sarcopenia. Both conditions are associated with renal alterations in energy metabolism and lower tissue ATP levels secondary to mitochondrial dysfunction and reduced mitochondrial number.

KEYWORDS:

CKD; Mitochondria; Obesity; Renal Energy; Sarcopenia

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