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Kidney Week

Abstract: PO2484

Time-Restricted Feeding Ameliorates Fibrosis by Restoring Disrupted Peripheral Clock in Adenine-Induced CKD Model

Session Information

Category: CKD (Non-Dialysis)

  • 2103 CKD (Non-Dialysis): Mechanisms

Authors

  • Fang, Yina, Korea University Anam Hospital, Seoul, Korea (the Republic of)
  • Oh, Sewon, Korea University Anam Hospital, Seoul, Korea (the Republic of)
  • Yang, Jihyun, Korea University Anam Hospital, Seoul, Korea (the Republic of)
  • Yoon Sook, Ko, Korea University Anam Hospital, Seoul, Korea (the Republic of)
  • Lee, Hee Young, Korea University Anam Hospital, Seoul, Korea (the Republic of)
  • Jo, Sang-Kyung, Korea University Anam Hospital, Seoul, Korea (the Republic of)
  • Cho, Won-Yong, Korea University Anam Hospital, Seoul, Korea (the Republic of)
  • Kim, Myung-Gyu, Korea University Anam Hospital, Seoul, Korea (the Republic of)
Background

Circadian disruption has recently been demonstrated to be closely associated with various metabolic diseases. Time restricted feeding (TRF) is a dietary strategy that limit the time of eating to a window of 4-12hr per day and has been shown to resynchronize peripheral clock. In this study, we aimed to investigate the relationship between circadian disruption and chronic kidney disease (CKD). We also tested whether TRF confer renoprotective effect via restoration of peripheral clock.

Methods

First, to determine the effect of CKD on circadian rhythm in the kidney, oscillation of several peripheral clock genes (Bmal1, Per1, CLOCK and Rev-erbα) as well as physiologic parameters (GFR, transporter protein expression and urine output) were compared between control and adenine induced CKD mice. To determine the role of circadian disruption on CKD progression, renal function and fibrosis were compared between WT and Bmal-1 knockout mice. In addition, adenine-induced CKD mice were given either a 24-hour ad libitum diet or a TRF for 8 weeks and the effect of TRF on CKD progression as well as oscillation of peripheral clock genes were measured.

Results

Adenine induced CKD mice showed disrupted oscillation of peripheral clock genes (Bmal1, Per1, CLOCK and Rev-erbα) and this was associated with loss of rhythmic oscillations of glomerular filtration rate, tubular functions and urine output. Meanwhile, more severe fibrosis and lower GFR were observed in Bmal1 (principal driver of molecular clock) knockout mice compared to WT mice, showing a bidirectional relationship between disturbed circadian rhythm and CKD progression. TRF in adenine induced CKD mice significantly suppressed interstitial inflammation as well as cell cycle arrest and ultimately ameliorated worsening of renal function and fibrosis. These changes were accompanied by partial restoration of disturbed oscillation of peripheral clock genes, suggesting that renoprotective effect of TRF is partially mediated by restoration of peripheral clock.

Conclusion

Our data demonstrated a unique bidirectional relationship between the circadian disruption and CKD and suggest that disruption of peripheral clock might contribute to CKD progression. The renoprotective effect of TRF might be mediated via resynchronizing disrupted peripheral clock in the kidney.