Obesity-promoting and anti-thermogenic effects of neutrophil gelatinase-associated lipocalin in mice

Sci Rep. 2017 Nov 14;7(1):15501. doi: 10.1038/s41598-017-15825-4.


Neutrophil gelatinase-associated lipocalin (NGAL, lipocalin 2 or LCN2) is an iron carrier protein whose circulating level is increased by kidney injury, bacterial infection and obesity, but its metabolic consequence remains elusive. To study physiological role of LCN2 in energy homeostasis, we challenged female Lcn2 knockout (KO) and wild-type (WT) mice with high fat diet (HFD) or cold exposure. Under normal diet, physical constitutions of Lcn2 KO and WT mice were indistinguishable. During HFD treatment, Lcn2 KO mice exhibited larger brown adipose tissues (BAT), consumed more oxygen, ate more food and gained less body weights as compared to WT mice. When exposed to 4 °C, KO mice showed higher body temperature and more intense 18F-fluorodeoxyglucose uptake in BAT, which were cancelled by β3 adrenergic receptor blocker or iron-loaded (but not iron-free) LCN2 administration. These findings suggest that circulating LCN2 possesses obesity-promoting and anti-thermogenic effects through inhibition of BAT activity in an iron-dependent manner.

MeSH terms

  • Adipose Tissue, Brown / drug effects
  • Adipose Tissue, Brown / metabolism*
  • Adipose Tissue, Brown / pathology
  • Adrenergic beta-3 Receptor Antagonists / pharmacology
  • Animals
  • Biological Transport
  • Cold Temperature
  • Diet, High-Fat / adverse effects
  • Eating / genetics
  • Energy Metabolism / genetics
  • Enterobactin / pharmacology
  • Female
  • Fluorodeoxyglucose F18 / metabolism
  • Gene Expression Regulation
  • Lipocalin-2 / blood
  • Lipocalin-2 / genetics*
  • Mice
  • Mice, Knockout
  • Obesity / etiology
  • Obesity / genetics*
  • Obesity / metabolism
  • Obesity / pathology
  • Oxygen Consumption / genetics
  • Propanolamines / pharmacology
  • RNA, Messenger / genetics*
  • RNA, Messenger / metabolism
  • Receptors, Adrenergic, beta-3 / genetics
  • Receptors, Adrenergic, beta-3 / metabolism
  • Signal Transduction
  • Thermogenesis / genetics*


  • 3-(2-ethylphenoxy)-1-(1,2,3,4-tetrahydronaphth-1-ylamino)-2-propanol oxalate
  • Adrenergic beta-3 Receptor Antagonists
  • Lipocalin-2
  • Propanolamines
  • RNA, Messenger
  • Receptors, Adrenergic, beta-3
  • Fluorodeoxyglucose F18
  • Lcn2 protein, mouse
  • Enterobactin
  • ferrienterochelin