<p>High-fat diet-induced kidney alterations in rats with metabolic syndrome: endothelial dysfunction and decreased antioxidant defense</p>

Abstract

This study aimed to investigate changes in renal function and the AGE-RAGE axis in the kidney of a non-genetic animal model of metabolic syndrome (MetS) induced by high-fat diet (HFD). Additionally, we evaluated the protective effect of pyridoxamine (PM), a vitamin B6 analog with anti-AGE effects, in the context of diet-related renal endothelial dysfunction. Methodology: In Wistar rats, the MetS animal model was induced by 20 or 28 weeks of HFD feeding. When indicated, a subgroup of animals was treated daily with PM (60 mg/kg) for 2 months. Tissue perfusion in renal microcirculation was examined by laser speckle contrast imaging. Oxidative stress was analyzed by thiobarbituric acid reactive species and the inflammatory markers by ELISA (TNF-α and IL-1β). Reverse transcription polymerase chain reaction was used to analyze eNOs, IL-6, vascular cell adhesion molecule (VCAM), NADPH oxidase subunit 47 (N47), catalase, and receptor for AGE (RAGE) gene expression. Results: Wistar rats fed a HFD showed negligible alteration in renal function, decrease in catalase mRNA transcripts and catalase enzyme activity compared to control (CTL) animals. Increased levels of IL-1β were observed in the kidney of MetS-induced rats. HFD-fed rats exhibited kidney endothelial dysfunction, with no significant differences in basal microvascular blood flow. PM significantly improved kidney vasorelaxation in HFD-fed rats. eNOS, VCAM, and RAGE gene expression and AGE content were not altered in kidneys of HFDinduced MetS rats in comparison to CTLs. Conclusions: Our findings suggest that HFD-induced microvascular dysfunction precedes the decline in renal function, and could be related to antioxidant machinery defects and inflammation activation in the kidney. PM showed a vasoprotective effect, and thus, could be an important contributory factor in ameliorating diet-induced renal damage.

Crescent-Like Lesions as an Early Signature of Nephropathy in a Rat Model of Prediabetes Induced by a Hypercaloric Diet

“…Concerning renal function, the prediabetic animals showed unchanged values of serum, urine and clearance of creatinine and uric acid, despite reduced BUN values which could be explained by the reduced protein consumption when compared with the control animals. These results are in agreement with other studies in Wistar rats under longstanding HFD that were unable to show marked changes on renal function markers [40]. The absence of changes in creatinine until a significant part of the glomeruli is already affected (it is estimated about 50%) is a known fact that has been portrayed as a limitation of the classic markers of renal function assessment, strongly recommending better markers of early renal dysfunction [12,13].…”

Pyridoxamine and Caloric Restriction Improve Metabolic and Microcirculatory Abnormalities in Rats with Non-Alcoholic Fatty Liver Disease

“…PM has proven effective against both systemic and hepatic changes in obesity-associated NAFLD [21]. A previous study by our group demonstrated that PM is able to reduce BW, liver leukocyte recruitment, and oxidative damage in animals presenting NAFLD [59].…”

Diet-Induced Rodent Models of Diabetic Peripheral Neuropathy, Retinopathy and Nephropathy

“…As discussed throughout the article, there are a variety of diets (with different components and percentages) that promote distinct degrees of dysfunction and lesion, due to distinct impact on the metabolic pathways underlying disease appearance and evolution, as it is recognized that diabetic complications are affected by various factors, including obesity, IR, hyperglycemia, and hyperlipidemia. Additionally, it is known that there are large variations in sensitivity/resistance to hypercaloric diets between different species (a paramount example is the C57BL/6 mice versus the Wistar rat when fed with HFD [80,81]) and even for different strains of the same species [79,91,103], namely, regarding sensitivity to the development of distinct complications, as reported for retinopathy and nephropathy in the ZSF1 rat under HFD [67,85]. Age is also a bias factor, as diabetic microvascular complications may have a distinct phenotype depending on the animals' age.…”

“…In fact, HFD-fed C57BL/6 mice develop features resembling human metabolic syndrome, such as obesity, hyperglycemia, hyperinsulinemia, hypertriglyceridemia, and hypertension, as well as increased UAE and renal glomerular lesions associated with extracellular matrix protein accumulation, together with impaired sodium handling, lipid accumulation, macrophage infiltration, and oxidative stress [80]. On the contrary, HFD-fed Wistar rats, even for a long period (20 to 28 weeks), are unable to develop major changes on renal function and basal microvascular blood flow, despite presenting kidney endothelial dysfunction and markers of increased renal oxidative stress and inflammation [81]. In order to overcome the absence of some of the main structural features of human DN seen in the models with HFD, researchers have been using HFD accompanied by a single high-dose STZ to aggravate pancreatic damage and induce a more advanced diabetic kidney disease.…”