Obesity-induced changes in kidney mitochondria and endoplasmic reticulum in the presence or absence of leptin.

OBESITY-INDUCED CHANGES IN KIDNEY MITOCHONDRIA AND ENDOPLASMIC RETICULUM IN THE PRESENCE OR ABSENCE OF LEPTIN. Am J Physiol Renal Physiol. 2015 Aug 19;:ajprenal.00188.2015 Authors: Munusamy S, do Carmo JM, Hosler JP, Hall JE Abstract We investigated obesity-induced changes in kidney lipid accumulation, mitochondrial function, and endoplasmic reticulum (ER) stress in the absence of hypertension, and the potential role of leptin in modulating these changes. We compared two normotensive genetic mouse models of obesity, leptin-deficient ob/ob mice and hyperleptinemic melanocortin-4 receptor deficient mice (LoxTB MC4R-/-), to their respective lean controls. Compared to controls, ob/ob and LoxTB MC4R-/- mice exhibit significant albuminuria, increased creatinine clearance and high renal triglyceride content. Renal ATP levels were decreased in both obesity models and mitochondria isolated from both models showed alterations that would lower mitochondrial ATP production. Mitochondria from hyperleptinemic LoxTB MC4R-/- mice kidneys respired NADH-generating substrates (including palmitate) at lower rates due to an apparent decrease in complex I activity, and these mitochondria showed oxidative damage. Kidney mitochondria of leptin-deficient ob/ob mice showed normal rates of respiration with no evidence of oxidative damage, but electron transfer was partially uncoupled from ATP synthesis. A 4-fold induction of C/EBP homologous protein (CHOP) exp...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research