Renal Endocannabinoid Dysregulation in Obesity-Induced Chronic Kidney Disease in Humans

Anna Permyakova, Ariel Rothner, Sarah Knapp, Alina Nemirovski, Danny Ben-Zvi, Joseph Tam

Research output: Contribution to journalArticlepeer-review

Abstract

The endocannabinoid system (ECS) regulates various physiological processes, including energy homeostasis and kidney function. ECS upregulation in obese animals and humans suggests a potential link to obesity-induced chronic kidney disease (CKD). However, obesity-induced ECS changes in the kidney are mainly studied in rodents, leaving the impact on obese humans unknown. In this study, a total of 21 lean and obese males (38–71 years) underwent a kidney biopsy. Biochemical analysis, histology, and endocannabinoid (eCB) assessment were performed on kidney tissue and blood samples. Correlations between different parameters were evaluated using a comprehensive matrix. The obese group exhibited kidney damage, reflected in morphological changes, and elevated kidney injury and fibrotic markers. While serum eCB levels were similar between the lean and obese groups, kidney eCB analysis revealed higher anandamide in obese patients. Obese individuals also exhibited reduced expression of cannabinoid-1 receptor (CB1R) in the kidney, along with increased activity of eCB synthesizing and degrading enzymes. Correlation analysis highlighted connections between renal eCBs, kidney injury markers, obesity, and related pathologies. In summary, this study investigates obesity’s impact on renal eCB “tone” in humans, providing insights into the ECS’s role in obesity-induced CKD. Our findings enhance the understanding of the intricate interplay among obesity, the ECS, and kidney function.

Original languageEnglish
Article number13636
JournalINTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume24
Issue number17
DOIs
StatePublished - Sep 2023

Keywords

  • chronic kidney disease
  • endocannabinoid system
  • obesity

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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