A low-salt diet increases the expression of renal sirtuin 1 through activation of the ghrelin receptor in rats.
Previous studies have shown that sirtuin 1 (Sirt1) is renoprotective; however, details regarding its distribution and functions in the kidney remain unknown. Here, we demonstrated that Sirt1 was mainly expressed in the tubulointerstitial cells of normal rat kidneys and was co-localized with aquaporin 2, indicating it may be involved in water/salt regulation. Renal Sirt1 expression increased in the non-glomerular cytoplasmic portion of the kidney after a 24-h fast, but no significant changes in Sirt1 expression occurred after water loading (50 mL/kg) or 24-h water deprivation. After consuming a low-salt (0.075%) or 60% calorie restriction diet for 7 days, Sirt1 expression in the rat kidney was significantly increased, whereas a high-salt (8%) diet did not change the level of Sirt1 expression. The low-salt diet also increased Sirt1 expression in the heart, muscle, brain, and fat tissues. The increased Sirt1 that was observed in rats on a low-salt diet was associated with increased ghrelin expression in the distal nephron, with both molecules exhibiting similar distribution patterns. An in vitro experiment suggested that ghrelin increases Sirt1 expression in cortical collecting duct cells by activating ghrelin receptors. Our study indicates that this 'ghrelin-Sirt1 system' may participate in regulating sodium reabsorption in the distal nephron.
Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.|Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan.
Shao-Yu
SY
Yang
Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan.|Graduate Institute of Physiology, National Taiwan University College of Medicine, Taipei, Taiwan.
Shuei-Liong
SL
Lin
Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan.|Department of Internal Medicine, National Taiwan University Hospital Yun-Lin Branch, Douliou City, Yunlin County, Taiwan.
Yung-Ming
YM
Chen
Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan.
Vin-Cent
VC
Wu
Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.|Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan.
Wei-Shiung
WS
Yang
Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan.
Kwan-Dun
KD
Wu
D000818:Animals; D051398:Aquaporin 1 / Q000378:metabolism; D051399:Aquaporin 2 / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D031204:Caloric Restriction; D002478:Cells, Cultured; D004039:Diet, Sodium-Restricted; D005215:Fasting / Q000378:metabolism; D007684:Kidney Tubules / Q000166:cytology / Q000378:metabolism*; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D054440:Receptors, Ghrelin / Q000378:metabolism*; D056564:Sirtuin 1 / Q000378:metabolism*; D015854:Up-Regulation
C496022:Aqp1 protein, rat; C496025:Aqp2 protein, rat; D051399:Aquaporin 2; D054440:Receptors, Ghrelin; D051398:Aquaporin 1; C488368:Sirt1 protein, rat; D056564:Sirtuin 1