Global analysis of kidney gene expression by RNA-Seq of aged CTRP1-deficient mice on high-fat diet
Aging and obesity profoundly influence organ system health by altering circulating levels of hormones, growth factors, and cytokines. C1q/TNF-related protein 1 (CTRP1) is an endocrine factor with important metabolic, cardiovascular, and renal functions. We sought to determine the impact of CTRP1 deficiency on heart and kidney function in the context of aging and obesity using aged and obese wild-type (WT) and Ctrp1 knockout (KO) mice fed a high-fat diet for eight months or longer. Surprisingly, no differences were observed in blood pressure, heart function, or vascular stiffness between genotypes. Loss of CTRP1, however, resulted in renal enlargement (relative to body weight), reduced urinary creatinine, elevated urinary total protein content and pH, and changes in renal gene expression affecting sugar, fat, and amino acid metabolism pathways. Assessment of glomerular integrity, the extent of podocyte foot process effacement, as well as renal response to water restriction and salt loading did not reveal significant differences between WT and Ctrp1-KO mice. Interestingly, blood platelet, white blood cell, neutrophil, lymphocyte, and eosinophil counts were significantly elevated, whereas mean corpuscular volume and hemoglobin were reduced in Ctrp1-KO mice. Cytokine profiling revealed increased circulating levels of CCL17 and TIMP-1 in KO mice. Compared to a previous study, our current data suggest that chronic high-fat feeding affects renal phenotypes differently than similarly aged mice fed a control low-fat diet, highlighting a diet-dependent contribution of CTRP1 deficiency to age-related changes in renal structure and function. Overall design: Kidney RNA sequenceing and bioinformatics analyesis was performed on age-matched 40 week-old wildtype (WT) and CTRP1-/- mice fed a high-fat diet, with 4 biological replicates for each genotype for a total of 8 mice. Thus, 4 KO mice were compared to 4 WT.