The Development of Dyslipidemia in Chronic Kidney Disease and Associated Cardiovascular Damage, and the Protective Effects of Curcuminoids.

Chronic kidney disease (CKD) is a health problem that is constantly growing. This disease presents a diverse symptomatology that implies complex therapeutic management. One of its characteristic symptoms is dyslipidemia, which becomes a risk factor for developing cardiovascular diseases and increases the mortality of CKD patients. Various drugs, particularly those used for dyslipidemia, consumed in the course of CKD lead to side effects that delay the patient's recovery. Therefore, it is necessary to implement new therapies with natural compounds, such as curcuminoids (derived from the Curcuma longa plant), which can cushion the damage caused by the excessive use of medications. This manuscript aims to review the current evidence on the use of curcuminoids on dyslipidemia in CKD and CKD-induced cardiovascular disease (CVD). We first described oxidative stress, inflammation, fibrosis, and metabolic reprogramming as factors that induce dyslipidemia in CKD and their association with CVD development. We proposed the potential use of curcuminoids in CKD and their utilization in clinics to treat CKD-dyslipidemia.

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

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 ß-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.

Leptin and adiponectin synthesis and secretion in mature 3T3-L1 adipocytes are differentially down-regulated by arsenic and palmitic acid exposure throughout different stages of adipogenesis.

AIMS: Arsenic is a risk factor for type 2 diabetes and cardiovascular disease. However, little is known about arsenic effects over adipocyte endocrine functionality, particularly for leptin and adiponectin, and about its interaction with dietary components, which are the main environmental regulators of adipose tissue functionality. The aim of this work was to evaluate leptin and adiponectin in mature 3T3-L1 adipocytes exposed to palmitate (simulating excess fat intake), arsenite, or both throughout two different stages of adipogenesis. MATERIAL AND METHODS: 3T3-L1 adipocytes were exposed starting from the beginning of its differentiation process during 11 d or once adipocytes were mature for 72 h. Adipokines secretion was evaluated by ELISA, intracellular protein levels and secreted adiponectin multimers by Western blot and mRNA abundance by qPCR. KEY FINDINGS: Leptin and adiponectin secretion decreased by arsenite alone or in combination with palmitate due to reduced gene and protein expression of both adipokines. However, leptin was impaired more at the transcriptional level, whereas affections to adiponectin were more relevant at the intracellular protein amount level with changes in the multimers proportion. The gene expression of several of their transcription factors was altered. Additionally, the magnitude of the effects depends on the adipocyte cell stage at which exposure began; adiponectin was more affected when exposure started from differentiation and leptin once adipocytes were mature. SIGNIFICANCE: These results in an in vivo model could be translated into less satiety and reduced insulin sensitivity.

Effects of arsenic on adipocyte metabolism: Is arsenic an obesogen?

The environmental obesogen model proposes that in addition to a high-calorie diet and diminished physical activity, other factors such as environmental pollutants and chemicals are involved in the development of obesity. Although arsenic has been recognized as a risk factor for Type 2 Diabetes with a specific mechanism, it is still uncertain whether arsenic is also an obesogen. The impairment of white adipose tissue (WAT) metabolism is crucial in the onset of obesity, and distinct studies have evaluated the effects of arsenic on it, however only in some of them for obesity-related purposes. Thus, the known effects of arsenic on WAT/adipocytes were integrated based on the diverse metabolic and physiological processes that occur in WAT and are altered in obesity, specifically: adipocyte growth, adipokine secretion, lipid metabolism, and glucose metabolism. The currently available information suggests that arsenic can negatively affect WAT metabolism, resulting in arsenic being a potential obesogen.