Aging and chronic high-fat feeding negatively affect kidney size, function, and gene expression in CTRP1-deficient mice
| Autor: | Dylan C. Sarver, G. William Wong, Susana Rodriguez, Dan E. Berkowitz, Jennifer L. Pluznick, Hannah C. Little, Paride Fenaroli, Michael Delannoy, C. Conover Talbot, Avi Z. Rosenberg, Stefanie Y. Tan, Parnaz Daneshpajouhnejad, Sandeep Jandu |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty Aging Genotype Physiology 030204 cardiovascular system & hematology Biology Affect (psychology) Diet High-Fat Kidney 03 medical and health sciences 0302 clinical medicine Adipokines Physiology (medical) Internal medicine Gene expression medicine Deficient mouse High fat feeding Endocrine system Animals Obesity Mice Knockout Tissue Inhibitor of Metalloproteinase-1 Age Factors Metabolism Hypertrophy medicine.disease Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure Endocrinology Phenotype Gene Expression Regulation Female Kidney Diseases Chemokine CCL17 Research Article |
| Zdroj: | Am J Physiol Regul Integr Comp Physiol |
| ISSN: | 1522-1490 |
| Popis: | C1q/TNF-related protein 1 (CTRP1) is an endocrine factor with metabolic, cardiovascular, and renal functions. We previously showed that aged Ctrp1-knockout (KO) mice fed a control low-fat diet develop renal hypertrophy and dysfunction. Since aging and obesity adversely affect various organ systems, we hypothesized that aging, in combination with obesity induced by chronic high-fat feeding, would further exacerbate renal dysfunction in CTRP1-deficient animals. To test this, we fed wild-type and Ctrp1-KO mice a high-fat diet for 8 mo or longer. Contrary to our expectation, no differences were observed in blood pressure, heart function, or vascular stiffness between genotypes. Loss of CTRP1, however, resulted in an approximately twofold renal enlargement (relative to body weight), ∼60% increase in urinary total protein content, and elevated pH, and changes in renal gene expression affecting metabolism, signaling, transcription, cell adhesion, solute and metabolite transport, and inflammation. 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 genotypes. 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 with our previous study, 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. |
| Databáze: | OpenAIRE |
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