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

被引：26

作者：

Ishii, Akira ^{[1
]}

Katsuura, Goro ^{[2
]}

Imamaki, Hirotaka ^{[1
,3
]}

Kimura, Hiroyuki ^{[4
]}

Mori, Keita P. ^{[1
]}

Kuwabara, Takashige ^{[5
]}

Kasahara, Masato ^{[6
]}

Yokoi, Hideki ^{[1
]}

Ohinata, Kousaku ^{[7
]}

Kawanishi, Tomoko ^{[8
]}

Tsuchida, Junichi ^{[9
,10
]}

Nakamoto, Yuji ^{[11
]}

Nakao, Kazuwa ^{[12
]}

Yanagita, Motoko ^{[1
,9
]}

Mukoyama, Masashi ^{[5
]}

Mori, Kiyoshi ^{[9
,13
,14
]}

机构：

[1] Kyoto Univ, Grad Sch Med, Dept Nephrol, Kyoto, Japan

[2] Kagoshima Univ, Dept Psychosomat Internal Med, Grad Sch Med & Dent Sci, Kagoshima, Japan

[3] Hirakata Kohsai Hosp, Dept Nephrol, Hirakata, Osaka, Japan

[4] Kyoto Pharmaceut Univ, Dept Analyt & Bioinorgan Chem, Kyoto, Japan

[5] Kumamoto Univ, Grad Sch Med Sci, Dept Nephrol, Kumamoto, Japan

[6] Nara Med Univ, Inst Clin & Translat Sci, Kashihara, Nara, Japan

[7] Kyoto Univ, Grad Sch Agr, Div Food Sci & Biotechnol, Uji, Japan

[8] Ohkubo Hosp, Dept Nephrol, Tokyo, Japan

[9] Kyoto Univ, Med Innovat Ctr, TMK Project, Grad Sch Med, Kyoto, Japan

[10] Mitsubishi Tanabe Pharma Corp, Innovat Res Div, Res Unit Nephrol & Endocrinol Sci, Sohya Ku, Toda, Saitama, Japan

[11] Kyoto Univ, Grad Sch Med, Dept Diagnost Imaging & Nucl Med, Kyoto, Japan

[12] Kyoto Univ, Grad Sch Med, Med Innovat Ctr, TK Project, Kyoto, Japan

[13] Univ Shizuoka, Sch Pharmaceut Sci, Dept Mol & Clin Pharmacol, Shizuoka, Japan

[14] Shizuoka Prefectural Gen Hosp, Dept Nephrol & Kidney Res, Shizuoka, Japan

来源：

SCIENTIFIC REPORTS | 2017年 / 7卷

基金：

日本学术振兴会;

关键词：

BROWN ADIPOSE-TISSUE; INSULIN-RESISTANCE; COLD-EXPOSURE; UNCOUPLING PROTEIN-1; NATRIURETIC PEPTIDE; RENAL INJURY; MOUSE MODEL; RECEPTOR; KIDNEY; DIET;

D O I：

10.1038/s41598-017-15825-4

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 degrees C, KO mice showed higher body temperature and more intense F-18-fluorodeoxyglucose uptake in BAT, which were cancelled by beta 3 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.

引用

页数：11

共 54 条

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