Mechanisms and consequences of hypertriglyceridemia and cellular lipid accumulation in chronic kidney disease and metabolic syndrome

Abstract

Hypertriglyceridemia and intracellular lipid overload are commonly present in both the chronic kidney disease (CKD) and metabolic syndrome. Hypertriglyceridemia in the metabolic syndrome arises mostly from increased lipoprotein synthesis, while that in the CKD is mainly caused by decreased catabolism. In metabolic syndrome, enhanced plasma levels of free fatty acids and triglyceride (TG) may lead to intracellular fatty acid accumulation in the kidney. However, the mechanisms by which intracellular lipid accumulation occurs in the dieased glomeruli have not been established. I provide evidence that binding/uptake of TG-rich very low-density lipoprotein by glomerular cells is increased in CKD, leading to increased endocytic accumulation of TG. I also provide evidence that cellular damage by fatty acid accumulation in the kidney is particularly severe in podocytes, leading to apoptosis and resulting in glomerulosclerosis. Collectively, these data bring new mechanistic insights into cellular lipid overload and lipotoxicity in CKD.