Obesity causes renal mitochondrial dysfunction and energy imbalance and accelerates chronic kidney disease in mice

Am J Physiol Renal Physiol. 2019 Oct 1;317(4):F941-F948. doi: 10.1152/ajprenal.00203.2019. Epub 2019 Aug 14.


Obesity and metabolic syndrome are well-known risk factors for chronic kidney disease (CKD); however, 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 after 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 mo) and earlier mortality in pound mice compared with controls. After 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 CKD 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: chronic kidney disease; mitochondria; obesity; renal energy; sarcopenia.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adenine / toxicity
  • Adenosine Triphosphate / metabolism
  • Animals
  • Energy Metabolism*
  • Kidney / metabolism*
  • Kidney Function Tests
  • Kidney Tubules / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Obese
  • Mitochondria / metabolism*
  • Obesity / complications*
  • Obesity / metabolism*
  • Renal Insufficiency, Chronic / complications*
  • Renal Insufficiency, Chronic / metabolism*
  • Sarcopenia / etiology
  • Sarcopenia / metabolism


  • Adenosine Triphosphate
  • Adenine