Lipotoxicity in Kidney, Heart, and Skeletal Muscle Dysfunction

Nutrients. 2019 Jul 20;11(7):1664. doi: 10.3390/nu11071664.

Abstract

Dyslipidemia is a common nutritional and metabolic disorder in patients with chronic kidney disease. Accumulating evidence supports the hypothesis that prolonged metabolic imbalance of lipids leads to ectopic fat distribution in the peripheral organs (lipotoxicity), including the kidney, heart, and skeletal muscle, which accelerates peripheral inflammation and afflictions. Thus, lipotoxicity may partly explain progression of renal dysfunction and even extrarenal complications, including renal anemia, heart failure, and sarcopenia. Additionally, endoplasmic reticulum stress activated by the unfolded protein response pathway plays a pivotal role in lipotoxicity by modulating the expression of key enzymes in lipid synthesis and oxidation. Here, we review the molecular mechanisms underlying lipid deposition and resultant tissue damage in the kidney, heart, and skeletal muscle, with the goal of illuminating the nutritional aspects of these pathologies.

Keywords: kidney; lipotoxicity; sarcopenia; skeletal muscle; uremia.

Publication types

  • Review

MeSH terms

  • Dyslipidemias / complications*
  • Heart Diseases / etiology*
  • Heart Diseases / metabolism
  • Humans
  • Kidney Diseases / etiology*
  • Kidney Diseases / metabolism
  • Lipid Metabolism*
  • Muscle, Skeletal / metabolism
  • Muscular Diseases / etiology*
  • Muscular Diseases / metabolism