Renal lipotoxicity: Insights from experimental models

• Published in: Clinical and experimental pharmacology & physiology Vol. 48; no. 12; pp. 1579 - 1588
• Main Authors: Castro, Barbara Bruna Abreu, Foresto‐Neto, Orestes, Saraiva‐Camara, Niels Olsen, Sanders‐Pinheiro, Helady
• Format: Journal Article
• Language: English
• Published: Australia Wiley Subscription Services, Inc 01.12.2021
• Subjects: Accumulation; Adipose tissue; Animals; Disease Models, Animal; Endoplasmic reticulum; Fatty acids; Fibrosis; high‐fat diet; Humans; hyperlipidaemia; Insulin; Insulin resistance; Kidney - metabolism; Kidney - pathology; Kidney diseases; Kidney Diseases - etiology; Kidney Diseases - metabolism; Kidney Diseases - pathology; Kidneys; Lipid Metabolism; lipid metabolism disorders; Lipids; Mitochondria; Mitochondria - metabolism; Mitochondria - pathology; Morphology; Obesity; Obesity - metabolism; Obesity - pathology; Organs; Oxidation resistance; Oxidative stress; Renal function; Storage capacity; Target recognition; Therapeutic targets; Triglycerides; fatty acids; hyperlipidaemia; kidney diseases; lipid metabolism disorders; high-fat diet
• ISSN: 0305-1870; 1440-1681; 1440-1681
• DOI: 10.1111/1440-1681.13556

In recent decades, there has been a progressive increase in the prevalence of obesity and chronic kidney disease. Renal lipotoxicity has been associated with obesity. Although lipids play fundamental physiological roles, the accumulation of lipids in kidney cells may cause dysfunction and/or renal fibrosis. Adipose tissue that exceeds their lipid storage capacity begins to release triglycerides into the bloodstream that can get stored in several organs, including the kidneys. The mechanisms underlying renal lipotoxicity involve intracellular lipid accumulation and organelle dysfunction, which trigger oxidative stress and inflammation that consequently result in insulin resistance and albuminuria. However, the specific pathways involved in renal lipotoxicity have not yet been fully understood. We aimed to summarize the current knowledge on the mechanisms by which lipotoxicity affects the renal morphology and function in experimental models of obesity. The accumulation of fatty acids in tubular cells has been described as the main mechanism of lipotoxicity; however, lipids and their metabolism also affect the function and the survival of podocytes. In this review, we presented indication of mitochondrial, lysosomal and endoplasmic reticulum alterations involved in kidney damage caused by obesity. The kidney is vulnerable to lipotoxicity, and studies of the mechanisms underlying renal injury caused by obesity can help identify therapeutic targets to control renal dysfunction. Changes in lipid metabolism cause damage to the function and morphology of the kidneys. Defective mitochondrial oxidation and endoplasmic reticulum stress are associated with kidney damage caused by obesity. Studies of the mechanisms underlying renal injury caused by obesity can help identify therapeutic targets to control renal dysfunction.