Lipotoxicity as a trigger factor of renal disease

In the last few decades, rapid changes in lifestyle have led to an alarming increase in the prevalence of obesity and obesity-associated complications. Obese patients are at increased risk of developing hypertension, heart disease, insulin resistance, dyslipidemia, type 2 diabetes and kidney disease. The surplus of calories is normally stored as triglycerides in adipose tissue. However, excess lipids can also accumulate ectopically in other organs, including the kidney, contributing to their damage through toxic processes named lipotoxicity. The kidney is negatively affected by dyslipidemia, lipid accumulation and changes in circulating adipokines that bring about alterations in renal lipid metabolism and promote insulin resistance, generation of reactive oxygen species and endoplasmic reticulum stress, ultimately leading to alterations in the glomerular filtration barrier and renal failure. This review focuses on the pathogenic molecular mechanisms associated with renal lipotoxicity, and presents new insights about potential new therapeutic targets and biomarkers such as microRNAs and long non-coding RNAs, of relevance for the early detection of lipid-associated kidney disease.