Db/db Obese Mice Exhibit Enhanced Phosphorylation of p38, ERK1/2 and AKT in the Kidney
Haque MZ, Kumar V, Bettahi I, Palaniyandi SS, Young MS, Mohammad RM, and Abou Samra AB. Db/db obese mice exhibit enhanced phosphorylation of p38, ERK1/2 and AKT in the kidney. FASEB Journal 2018; 32(1 Suppl):719.6.
Altered metabolic states due to obesity and diabetes have a direct impact on renal structure and function. Obesity and diabetes leads to several key morphological, subcellular fibrotic remodeling, nephropathy and renal failure. However the clear signaling mechanism is not known. Leptin receptor deficiency is associated with obesity and hypercholesterolemia. We showed that acute cholesterol depletion increased cellular function and phosphorylation of p38, ERK and AKT kinases. Hence we hypothesized that obesity enhances phosphorylation of p38, ERK1/2 and AKT kinases in the kidney. To test our hypothesis we used kidneys from 25 weeks old four leptin receptor deficient db/db obese mice and their age matched four c57BL6 (wild type) mice. Transverse slices were made from similar position of all kidneys. Kidney slices were chopped into very small pieces and homogenized under the ice cold lysis buffer with protease and phospahtase inhibitors. The low spin pellets were discarded and the supernatants were collected. Kidney lysates were run through 7-12% poly acrylamide gel electrophoresis. Phosphorylations of p38, ERK1/2 and AKT were measured using western blot and cell signaling antibodies. The results were normalized to β-actin as a control for protein loading using NIH image J software. Data of phospho proteins expressed in arbitrary units for p38 (14477 ±1703 vs. 22488±2773, p<0.03), ERK1/2 (12408 ±1965 vs. 21807±1467, p<0.01) and AKTThr308 (10173 ±462 vs. 18250±1198, p<0.01) were more in obese db/db mice compared to wild type mice. Total p38, ERK1/2 and AKT were not different between db/db and wild type mice. We conclude that obesity is associated with enhanced phosphorylation of p38, ERK and AKTThr308 which could be associated with altered renal structure and function.