Lipocalin-2 derived from adipose tissue mediates aldosterone-induced renal injury

JCI Insight. 2018 Sep 6;3(17):e120196. doi: 10.1172/jci.insight.120196.


Lipocalin-2 is not only a sensitive biomarker, but it also contributes to the pathogenesis of renal injuries. The present study demonstrates that adipose tissue-derived lipocalin-2 plays a critical role in causing both chronic and acute renal injuries. Four-week treatment with aldosterone and high salt after uninephrectomy (ANS) significantly increased both circulating and urinary lipocalin-2, and it induced glomerular and tubular injuries in kidneys of WT mice. Despite increased renal expression of lcn2 and urinary excretion of lipocalin-2, mice with selective deletion of lcn2 alleles in adipose tissue (Adipo-LKO) are protected from ANS- or aldosterone-induced renal injuries. By contrast, selective deletion of lcn2 alleles in kidney did not prevent aldosterone- or ANS-induced renal injuries. Transplantation of fat pads from WT donors increased the sensitivity of mice with complete deletion of Lcn2 alleles (LKO) to aldosterone-induced renal injuries. Aldosterone promoted the urinary excretion of a human lipocalin-2 variant, R81E, in turn causing renal injuries in LKO mice. Chronic treatment with R81E triggered significant renal injuries in LKO, resembling those observed in WT mice following ANS challenge. Taken in conjunction, the present results demonstrate that lipocalin-2 derived from adipose tissue causes acute and chronic renal injuries, largely independent of local lcn2 expression in kidney.

Keywords: Adipose tissue; Inflammation; Mouse models; Nephrology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / chemically induced
  • Acute Kidney Injury / metabolism*
  • Acute Kidney Injury / pathology
  • Adipose Tissue / metabolism*
  • Adipose Tissue / pathology
  • Aldosterone / pharmacology*
  • Alleles
  • Animals
  • Biomarkers
  • Disease Models, Animal
  • Female
  • Fibrosis
  • Humans
  • Kidney / pathology
  • Lipocalin-2 / genetics
  • Lipocalin-2 / metabolism*
  • Lipocalin-2 / pharmacology
  • Lipocalin-2 / urine
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nephrectomy
  • Recombinant Proteins


  • Biomarkers
  • LCN2 protein, human
  • Lipocalin-2
  • Recombinant Proteins
  • Lcn2 protein, mouse
  • Aldosterone