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Aging and chronic high-fat feeding negatively affects kidney size, function, and gene expression in CTRP1-deficient mice.

Authors
  • Rodriguez, Susana1
  • Little, Hannah C1
  • Daneshpajouhnejad, Parnaz2
  • Fenaroli, Paride2
  • Tan, Stefanie Y1
  • Sarver, Dylan C1
  • Delannoy, Michael3
  • Talbot, C Conover Jr4
  • Jandu, Sandeep5
  • Berkowitz, Dan E5
  • Pluznick, Jennifer L6
  • Rosenberg, Avi Z7
  • Wong, G William1
  • 1 Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, Maryland; Center for Metabolism and Obesity Research, Johns Hopkins University School of Medicine, Baltimore, Maryland.
  • 2 Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States. , (United States)
  • 3 Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States. , (United States)
  • 4 Institute for Basic Biomedical Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States. , (United States)
  • 5 Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States. , (United States)
  • 6 Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States. , (United States)
  • 7 Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland; Kidney Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland.
Type
Published Article
Journal
AJP Regulatory Integrative and Comparative Physiology
Publisher
American Physiological Society
Publication Date
Oct 21, 2020
Identifiers
DOI: 10.1152/ajpregu.00139.2020
PMID: 33085906
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

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 affects various organ systems, we hypothesized that aging, in combination with obesity induced by chronic high-fat feeding, would further exacerbates renal dysfunction in CTRP1-deficient animals. To test this, we fed wild-type and Ctrp1 KO mice a high-fat diet for eight months 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 ~2-fold 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 to 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.

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