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

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 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.

SUBMITTER: Rodriguez S

PROVIDER: S-EPMC7847058 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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

Rodriguez Susana S Little Hannah C HC Daneshpajouhnejad Parnaz P Fenaroli Paride P Tan Stefanie Y SY Sarver Dylan C DC Delannoy Michael M Talbot C Conover CC Jandu Sandeep S Berkowitz Dan E DE Pluznick Jennifer L JL Rosenberg Avi Z AZ Wong G William GW

American journal of physiology. Regulatory, integrative and comparative physiology 20201021 1

C1q/TNF-related protein 1 (CTRP1) is an endocrine factor with metabolic, cardiovascular, and renal functions. We previously showed that aged <i>Ctrp1-</i>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-typ ...[more]

PMID: 33085906

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Dataset Information

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

Publications

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

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