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Empagliflozin Attenuates Obesity-Related Kidney Dysfunction and NLRP3 Inflammasome Activity Through the

Tongtong Ye1,2, Jingwen Zhang1,2, Di Wu1,2

  • 1Department of Endocrinology and Metabolism, Affiliated Hospital of Weifang Medical University, Weifang, China.

Frontiers in Endocrinology
|July 5, 2022
PubMed

Insights

Empagliflozin (EMPA) improves obesity-related kidney disease by reducing inflammation and enhancing the heme oxygenase-1 (HO-1)-adiponectin axis. This sodium-glucose cotransporter 2 inhibitor (SGLT2i) offers a novel mechanism for renal protection in obesity.

Area of Science:

  • Nephrology
  • Endocrinology
  • Metabolic Diseases

Background:

  • Obesity-related kidney disease (ORKD) is a growing concern with limited therapeutic options.
  • Sodium-glucose cotransporter 2 inhibitors (SGLT2i), like empagliflozin (EMPA), show cardiovascular and renal benefits in diabetes.
  • The role of EMPA in ORKD and its underlying mechanisms, particularly the heme oxygenase-1 (HO-1)-adiponectin axis, remains unclear.

Purpose of the Study:

  • To investigate the efficacy of EMPA in an animal model of obesity-related kidney disease.
  • To determine if EMPA modulates the renal HO-1-adiponectin axis in the context of obesity.
  • To explore the impact of EMPA on renal inflammation, specifically NLRP3 inflammasome activity.

Main Methods:

  • C57BL/6J mice were fed a high-fat diet (HFD) to induce obesity and kidney injury.
  • Mice received either a control diet, HFD, or HFD with EMPA treatment (10 mg/kg).
  • Renal function, metabolic parameters, lipotoxicity, NLRP3 inflammasome activity, and the HO-1-adiponectin axis were assessed.

Main Results:

  • HFD induced metabolic abnormalities and renal injury, characterized by albuminuria, morphological changes, and lipid accumulation.
  • EMPA treatment ameliorated metabolic disorders and attenuated lipotoxicity-induced renal injury in HFD mice.
  • EMPA upregulated the renal HO-1-adiponectin axis and reduced NLRP3 inflammasome activity.

Conclusions:

  • Empagliflozin effectively improves obesity-related kidney disease in a mouse model.
  • EMPA exerts renal protection by reducing NLRP3 inflammasome activity and enhancing the HO-1-adiponectin axis.
  • These findings suggest a novel mechanism for SGLT2i-mediated renal protection in obesity.
Keywords:
EmpagliflozinHO-1NLRP3kidney diseaseobesity

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