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

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

Author information

1
Department of Nephrology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
2
Department of Psychosomatic Internal Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
3
Department of Nephrology, Hirakata Kohsai Hospital, Hirakata, Japan.
4
Department of Analytical and Bioinorganic Chemistry, Kyoto Pharmaceutical University, Kyoto, Japan.
5
Department of Nephrology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
6
Institute for Clinical and Translational Science, Nara Medical University, Kashihara, Japan.
7
Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Japan.
8
Department of Nephrology, Ohkubo Hospital, Tokyo, Japan.
9
TMK Project, Medical Innovation Center, Kyoto University Graduate School of Medicine, Kyoto, Japan.
10
Research Unit/Nephrological & Endocrinological Science, Sohyaku, Innovative Research Division, Mitsubishi Tanabe Pharma Corporation, Toda, Japan.
11
Department of Diagnostic Imaging and Nuclear Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.
12
TK Project, Medical Innovation Center, Kyoto University Graduate School of Medicine, Kyoto, Japan.
13
TMK Project, Medical Innovation Center, Kyoto University Graduate School of Medicine, Kyoto, Japan. kiyoshimori2001@gmail.com.
14
Department of Molecular and Clinical Pharmacology, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan. kiyoshimori2001@gmail.com.
15
Department of Nephrology and Kidney Research, Shizuoka General Hospital, Shizuoka, Japan. kiyoshimori2001@gmail.com.

Abstract

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.

PMID:
29138470
PMCID:
PMC5686189
DOI:
10.1038/s41598-017-15825-4
[Indexed for MEDLINE]
Free PMC Article

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