Therapeutic Effect of Curcumin on 5/6Nx Hypertriglyceridemia: Association with the Improvement of Renal Mitochondrial β-Oxidation and Lipid Metabolism in Kidney and Liver

Abstract

Chronic kidney disease (CKD) prevalence is constantly increasing, and dyslipidemia in this disease is characteristic, favoring cardiovascular events. However, the mechanisms of CKD dyslipidemia are not fully understood. The use of curcumin (CUR) in CKD models such as 5/6 nephrectomy (5/6Nx) has shown multiple beneficial effects, so it has been proposed to correct dyslipidemia without side effects. This work aimed to characterize CUR’s potential therapeutic effect on dyslipidemia and alterations in lipid metabolism and mitochondrial ß-oxidation in the liver and kidney in 5/6Nx. Male Wistar rats were subjected to 5/6Nx and progressed by 4 weeks; meanwhile, CUR (120 mg/kg) was administered for weeks 5 to 8. Our results showed that CUR reversed the increase in liver and kidney damage and hypertriglyceridemia induced by 5/6Nx. CUR also reversed mitochondrial membrane depolarization and β-oxidation disorders in the kidney and the increased lipid uptake and the high levels of proteins involved in fatty acid synthesis in the liver and kidney. CUR also decreased lipogenesis and increased mitochondrial biogenesis markers in the liver. Therefore, we concluded that the therapeutic effect of curcumin on 5/6Nx hypertriglyceridemia is associated with the restoration of renal mitochondrial ß-oxidation and the reduction in lipid synthesis and uptake in the kidneys and liver.

Antioxidant and anti-inflammatory effects of allicin in the kidney of an experimental model of metabolic syndrome

“…The effects on lipids were through increased expression of genes involved in lipolysis (hormone-sensitive lipase (HSL), adipose triglyceride lipase (ATGL) and lipoprotein lipase (LPL)), and in the signaling pathway of insulin (insulin receptor substrate 1 (IRS-1) and IRS-2). Also, allicin downregulated the expression of lipogenic genes (SREBP1, acetyl-CoA carboxylase (ACC), fatty acid synthase (FASN), stearoyl-CoA desaturase-1 (SCD-1), and activated receptor by peroxisome proliferator-γ (PPARγ)) ( Shi et al, 2019 ; Ashraf et al, 2005 ; Cannizzaro et al, 2017 ); this is particularly important as up-regulation of fatty acid synthesis is closely related with mitochondrial bioenergetics impairment in various models or renal damage, such as the induced by the unilateral ureteral obstruction, folic acid, and nephrectomy ( Ceja-Galicia et al, 2022 ; Martínez-Klimova et al, 2020 ; Kang et al, 2015 ). Furthermore, our results showed that allicin improved the electron flow in the mitochondria suggesting that restoration of mitochondrial bioenergetics could lead to protective effects in renal and plasma lipids.…”

Mitochondrial Impairment: A Link for Inflammatory Responses Activation in the Cardiorenal Syndrome Type 4

“…Since early CKD stages, nephron segments like proximal tubules increase their lipid levels [96,102] and the fatty acid uptake protein CD36 levels [102,104], associated with inflammatory pathways induction [105]. CKD lipotoxicity increases fatty acid levels in plasma and kidneys, especially palmitic acid [103,106,107]. Palmitic acid has been shown to inhibit the adenosine monophosphate (AMP)-activated protein kinase (AMPK) signaling, reducing mitochondrial function, and increasing mitochondrial ROS production to favor the NLRP3 inflammasome activation, caspase-1, IL-1β, and IL-18 production [107,108].…”

“…The higher fatty acid synthesis in CKD may also induce NLRP3 pathway activation by the fatty acid synthase (FASN) induction. This enzyme is upregulated in the remnant kidney of 5/6 nephrectomy rats [106], likely leading to upregulation of the expression of the inflammasome components: NLRP3, caspase-1, and pro-IL-1β [99]. Thus, renal mitochondria impairment could be an essential regulator of NLRP3 inflammasome activation during CKD.…”