Hypercaloric Diet Promotes Metabolic Disorders and Impaired Kidney Function

Abstract

Poor dietary habits such as overconsumption of hypercaloric diets characterized by a high content of fructose and fat are related to metabolic abnormalities development such as obesity, diabetes, and dyslipidemia. Accumulating evidence supports the hypothesis that if energy intake gradually exceeds the body's ability to store fat in adipose tissue, the prolonged metabolic imbalance of circulating lipids from endogenous and exogenous sources leads to ectopic fat distribution in the peripheral organs, especially in the heart, liver, and kidney. The kidney is easily affected by dyslipidemia, which induces lipid accumulation and reflects an imbalance between fatty acid supply and fatty acid utilization. This derives from tissue lipotoxicity, oxidative stress, fibrosis, and inflammation, resulting in structural and functional changes that lead to glomerular and tubule-interstitial damage. Some authors indicate that a lipid-lowering pharmacological approach combined with a substantial lifestyle change should be considered to treat chronic kidney disease (CKD). Also, the new therapeutic target identification and the development of new drugs targeting metabolic pathways involved with kidney lipotoxicity could constitute an additional alternative to combat the complex mechanisms involved in impaired kidney function. In this review article, we first provide the pathophysiological evidence regarding the impact of hypercaloric diets, such as high-fat diets and high-fructose diets, on the development of metabolic disorders associated with impaired renal function and the molecular mechanisms underlying tissue lipid deposition. In addition, we present the current progress regarding translational strategies to prevent and/or treat kidney injury related to the consumption of hypercaloric diets.

Keywords: Chronic kidney disease; dyslipidemia; high-fat diet; high-fructose corn syrup; lipid droplets; lipotoxicity.