Combined Intake of Fish Oil and D-Fagomine Prevents High-Fat High-Sucrose Diet-Induced Prediabetes by Modulating Lipotoxicity and Protein Carbonylation in the Kidney

Abstract

Obesity has been recognized as a major risk factor for chronic kidney disease, insulin resistance being an early common metabolic feature in patients suffering from this syndrome. This study aims to investigate the mechanism underlying the induction of kidney dysfunction and the concomitant onset of insulin resistance by long-term high-fat and sucrose diet feeding in Sprague Dawley rats. To achieve this goal, our study analyzed renal carbonylated protein patterns, ectopic lipid accumulation and fatty acid profiles and correlated them with biometrical and biochemical measurements and other body redox status parameters. Rats fed the obesogenic diet developed a prediabetic state and incipient kidney dysfunction manifested in increased plasma urea concentration and superior levels of renal fat deposition and protein carbonylation. An obesogenic diet increased renal fat by preferentially promoting the accumulation of saturated fat, arachidonic, and docosahexaenoic fatty acids while decreasing oleic acid. Renal lipotoxicity was accompanied by selectively higher carbonylation of proteins involved in the blood pH regulation, i.e., bicarbonate reclamation and synthesis, amino acid, and glucose metabolisms, directly related to the onset of insulin resistance. This study also tested the combination of antioxidant properties of fish oil with the anti-diabetic properties of buckwheat D-Fagomine to counteract diet-induced renal alterations. Results demonstrated that bioactive compounds combined attenuated lipotoxicity, induced more favorable lipid profiles and counteracted the excessive carbonylation of proteins associated with pH regulation in the kidneys, resulting in an inhibition of the progression of the prediabetes state and kidney disease.

Dietary Marine Oils Selectively Decrease Obesogenic Diet-Derived Carbonylation in Proteins Involved in ATP Homeostasis and Glutamate Metabolism in the Rat Cerebellum

“…The cerebellar tissue used for this study comes from the same set of animals that was used in previous analyses [17][18][19]35,36]. Briefly, the experiments were carried out on male Sprague-Dawley rats (n = 36; aged 8-9 weeks in the beginning of experiment).…”

“…Detailed information on diet composition and fatty acid diet profiles are provided in Tables S1 and S2, respectively. Additionally, details about the health status of the rats and other experimental conditions can be found in the previous publications [17][18][19]35,36], with a summary of the most relevant data for the current investigation presented in Table S3.…”

“…The long-term intake of the HFHS diet induced a prediabetic state in rats, accompanied by systemic oxidative stress (Table S3). Prediabetic rats exhibited higher levels of protein carbonylation in the plasma, liver and kidneys [17,18,36]. The consumption of the HFHS diet also led to an increased accumulation of lipid peroxidation product and carbonylated proteins in the brain cortex [19].…”

“…This selectivity makes carbonylation crucial in metabolic control systems [16], especially in the CNS, where multiple processes are mediated by redox signaling [7]. Previous studies revealed that obesogenic diets selectively increased carbonylation of proteins participating in metabolic pathways crucial to liver and kidney function [17,18]. Recent findings have demonstrated that the intake of a high-fat and highsucrose diet results in increased carbonylation of specific target proteins in the brain cortex of rats [19].…”

“…The capacity of ω-3 PUFAs to protect the brain from oxidative stress has been described in several animal models [31][32][33][34]. Fish oil supplementation also demonstrated antioxidant properties and selective protection against carbonylation of specific proteins in the livers [17] and kidneys [18] of rats that had been fed an obesogenic diet. Very recently, similar effects were observed in the brain cortex [19].…”