Exercise training upregulates SIRT1 to attenuate inflammation and metabolic dysfunction in kidney and liver of diabetic db/db mice

Hung Wen Liu*, Hao Han Kao, Chi Hang Wu

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Chronic inflammation and metabolic dysregulation may eventually cause tissue damage in obesity-related diseases such as type 2 diabetes. The effects of SIRT1 on integration of metabolism and inflammation may provide a therapeutic target for treatment of obesity-related diseases. We examined the underlying mechanism of moderate intensity aerobic exercise on kidney and liver in obese diabetic db/db mice, mainly focusing on inflammation and metabolic dysfunction. Methods: Functional and morphological alterations and metabolic and inflammatory signaling were examined in type 2 diabetic db/db mice with or without exercise training (5.2 m/min, 1 h/day, and 5 days/week for a total of 8 weeks). Results: Exercise training prevented weight gain in db/db + Ex mice, but it did not reduce glucose and insulin levels. Exercise lowered serum creatinine, urea, and triglyceride levels and hepatic AST and ALT activity in db/db + Ex mice. Reduced kidney size and morphological alterations including decreased glomerular cross-sectional area and hepatic macrovesicles were observed in db/db + Ex mice compared with untrained db/db mice. Mechanistically, preventing loss of SIRT1 through exercise was linked to reduced acetylation of NF-κB in kidney and liver of db/db + Ex mice. Exercise increased citrate synthase and mitochondrial complex I activity, subunits of mitochondrial complexes (I, II, and V) and PGC1α at protein level in kidney of db/db + Ex mice compared with non-exercise db/db mice. Changes in enzyme activity and subunits of mitochondrial complexes were not observed in liver among three groups. Conclusion: Exercise-induced upregulation of SIRT1 attenuates inflammation and metabolic dysfunction, thereby alleviating the progression of diabetic nephropathy and hepatic steatosis in type 2 diabetes mellitus.

Original languageEnglish
Article number22
JournalNutrition and Metabolism
Volume16
Issue number1
DOIs
Publication statusPublished - 2019 Apr 2

Keywords

  • Diabetic db/db mice
  • Mitochondrial function
  • Moderate exercise
  • NF-κB
  • SIRT1

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics

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