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A low-salt diet increases the expression of renal sirtuin 1 through activation of the ghrelin receptor in rats.

ABSTRACT: 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.

SUBMITTER: Yang SY

PROVIDER: S-EPMC5013391 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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A low-salt diet increases the expression of renal sirtuin 1 through activation of the ghrelin receptor in rats.

Yang Shao-Yu SY Lin Shuei-Liong SL Chen Yung-Ming YM Wu Vin-Cent VC Yang Wei-Shiung WS Wu Kwan-Dun KD

Scientific reports 20160907

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 S ...[more]

PMID: 27600292

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Project description:Although activation of sirtuin-1 (SIRT1) has been shown to protect the kidney from acute injury, its role in renal fibrosis remains controversial since both inhibition and activation of SIRT1 have been reported to attenuate renal fibrosis. To resolve this conflict, we further examined the effect of SIRT1 activators on the activation of renal interstitial fibroblasts and development of renal fibrosis in vivo and in vitro. In a murine model of renal fibrosis induced by unilateral ureteral obstruction, administration of SRT1720 (N-[2-[3-(piperazin-1-ylmethyl)imidazo[2,1-b][1,3]thiazol-6-yl]phenyl]quinoxaline-2-carboxamide), a potent activator of SIRT1, accelerated deposition of collagen fibrils and increased expression of fibroblast activation markers (?-smooth muscle actin [?-SMA], collagen I, and fibronectin) in the obstructive kidney of mice. In cultured rat renal interstitial fibroblasts (NRK-49F), exposure of cells to SRT1720 or YK-3-237 (B-[2-methoxy-5-[(1E)-3-oxo-3-(3,4,5-trimethoxyphenyl)-1-propen-1-yl]phenyl]-boronic acid), another SIRT1 activator, also resulted in enhanced expression of ?-SMA and fibronectin. Mechanistic studies showed that augmentation of renal fibrogenesis by SRT1720 is associated with elevated phosphorylation of epidermal growth factor receptor (EGFR) and platelet-derived growth factor receptor ? (PDGFR?). SRT1720 treatment also increased the phosphorylation of signal transducer and activator of transcription 3 and protein kinase B in the fibrotic kidney and NRK-49F cells. However, SRT1720 treatment did not affect expression of proliferating cell nuclear protein, a proliferation marker and activation of extracellular signal regulated kinase 1/2 in vitro and in vivo. These results indicate that SIRT1-activating compounds can provoke renal fibrogenesis through a mechanism involved in the activation of EGFR and PDGFR signaling pathways and suggest that long-term use of SIRT1 activators risks the development and progression of chronic kidney disease.

Project description:Background/objectiveAn imbalance between energy intake and expenditure leads to obesity. Increasing metabolism and thermogenesis in brown adipose tissue (BAT) can help in overcoming obesity. Here, we investigated the effect of activation of transient receptor potential vanilloid subfamily 1 (TRPV1) in the upregulation of thermogenic proteins in BAT to counter diet-induced obesity.Subjects/methodsWe investigated the effect of dietary supplementation of capsaicin (CAP) (TRPV1 agonist) on the expression of metabolically important thermogenic proteins in BAT of wild-type and TRPV1-/- mice that received either a normal chow or high-fat (±CAP; TRPV1 activator) diet by immunoblotting. We measured the metabolic activity, respiratory quotient and BAT lipolysis.ResultsCAP antagonized high-fat diet (HFD)-induced obesity without decreasing energy intake in mice. HFD suppressed TRPV1 expression and activity in BAT and CAP countered this effect. HFD-feeding caused glucose intolerance, hypercholesterolemia and decreased the plasma concentration of glucagon-like peptide-1 and CAP countered these effects. HFD suppressed the expression of metabolically important thermogenic genes, ucp-1, bmp8b, sirtuin-1 (SIRT-1), PPARγ coactivator 1α and PR domain containing zinc finger protein 16 (prdm-16) in BAT and CAP prevented this effect. CAP increased the phosphorylation of SIRT-1 and induced an interaction between peroxisome proliferator activated receptor gamma (PPARγ) with PRDM-16. Further, CAP treatment, in vitro, decreased the acetylation of PRDM-16, which was antagonized by inhibition of TRPV1 by capsazepine, chelation of intracellular Ca2+ by cell permeable BAPTA-AM or the inhibition of SIRT-1 by EX527. Further, CAP supplementation, post HFD, promoted weight loss and enhanced the respiratory exchange ratio. CAP did not have any effect in TRPV1-/- mice.ConclusionsOur data show that activation of TRPV1 in BAT enhances the expression of SIRT-1, which facilitates the deacetylation and interaction of PPARγ and PRDM-16. These data suggest that TRPV1 activation is a novel strategy to counter diet-induced obesity by enhancing metabolism and energy expenditure.

Dataset Information

A low-salt diet increases the expression of renal sirtuin 1 through activation of the ghrelin receptor in rats.

Publications

A low-salt diet increases the expression of renal sirtuin 1 through activation of the ghrelin receptor in rats.

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