Underlying Mechanisms of Renal Lipotoxicity in Obesity

Nephron. 2019;143(1):28-32. doi: 10.1159/000494694. Epub 2019 Jan 9.


The recent and ongoing worldwide increase in the prevalence of obesity parallels the increase in the incidence of chronic kidney disease (CKD). This association suggests an implication of lipotoxicity in the development of kidney diseases. The increased influx of lipids into the kidney can be explained in the context of the "Adipose Tissue Expandability Hypothesis". This hypothesis states that the adipose tissue has a limited expansion capability, which is different for each individual, and once this limit is reached, the adipose tissue cannot store any more lipids and will thus release them into the bloodstream. The accumulation of lipids in the kidney is known as renal lipotoxicity. Renal lipotoxicity is known to cause detrimental effects on the kidney by several mechanisms of action including reclusion of pro-inflammatory factors, oxidative and ER stress development, insulin resistance (IR), lipid metabolism deregulation or renin-angiotensin aldosterone system overactivation. Isoform peroxisome proliferator-activated receptor gamma (PPARγ) seems to play an important role in the development of this lipotoxicity as proven by several studies in -animals and cultured cells. Thus, PPARγ agonists are of -interest in the therapeutic approach to treat CKD in the context of obesity. This review aims to summarize our current knowledge of the mechanism by which lipotoxicity affects renal structure and function using in vivo and in vitro models as examples focusing on PPARγ.

Keywords: Adipose tissue expandability; Chronic kidney disease; Lipotoxicity; Obesity; Peroxisome proliferator-activated receptor gamma.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Endoplasmic Reticulum Stress
  • Humans
  • Insulin Resistance
  • Kidney / metabolism*
  • Lipid Metabolism*
  • Obesity / complications*
  • Obesity / metabolism
  • Oxidative Stress
  • PPAR gamma / agonists
  • PPAR gamma / physiology
  • Renal Insufficiency, Chronic / etiology*


  • PPAR gamma