Lipocalin-2 deficiency impairs thermogenesis and potentiates diet-induced insulin resistance in mice.
Lipocalin-2 deficiency impairs thermogenesis and potentiates diet-induced insulin resistance in mice.
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作者：
Guo H;Jin D;Zhang Y;Wright W;Bazuine M;Brockman DA;Bernlohr DA;Chen X
脂质运载蛋白（LCN）2属于结合小疏水分子的低分子量分泌蛋白质的脂质运载蛋白亚家族。LCN 2最近被定性为一种脂肪源性细胞因子，其在遗传性肥胖啮齿动物的脂肪组织中表达上调。本研究的目的是研究LCN 2在体内饮食诱导的胰岛素抵抗和代谢稳态中的作用。在喂食高脂饮食（HFD）或普通饲料的LCN 2缺陷小鼠中评估全身胰岛素敏感性、适应性产热以及血清代谢和脂质谱。小鼠中LCN 2的分子破坏导致显著增强的饮食诱导的肥胖、血脂异常、脂肪肝疾病和胰岛素抵抗。LCN 2 −/−小鼠表现出受损的适应性产热和冷耐受性。白色和棕色脂肪组织、肝脏和肌肉中的基因表达模式表明，在HFD条件下，LCN 2 −/−小鼠的肝脏新生增加，线粒体氧化能力降低，脂质代谢受损，炎症状态增加。LCN 2在适应性体温调节和饮食诱导的胰岛素抵抗中具有新的作用。
Lipocalin (LCN) 2 belongs to the lipocalin subfamily of low–molecular mass–secreted proteins that bind small hydrophobic molecules. LCN2 has been recently characterized as an adipose-derived cytokine, and its expression is upregulated in adipose tissue in genetically obese rodents. The objective of this study was to investigate the role of LCN2 in diet-induced insulin resistance and metabolic homeostasis in vivo. Systemic insulin sensitivity, adaptive thermogenesis, and serum metabolic and lipid profile were assessed in LCN2-deficient mice fed a high-fat diet (HFD) or regular chow diet. The molecular disruption of LCN2 in mice resulted in significantly potentiated diet-induced obesity, dyslipidemia, fatty liver disease, and insulin resistance. LCN2−/− mice exhibit impaired adaptive thermogenesis and cold intolerance. Gene expression patterns in white and brown adipose tissue, liver, and muscle indicate that LCN2−/− mice have increased hepatic gluconeogenesis, decreased mitochondrial oxidative capacity, impaired lipid metabolism, and increased inflammatory state under the HFD condition. LCN2 has a novel role in adaptive thermoregulation and diet-induced insulin resistance.
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影响因子：
4.3
作者：
Okamatsu-Ogura, Yuko;Uozumi, Akihiro;Saito, Masayuki
通讯作者：
Saito, Masayuki
影响因子：
56.9
作者：
Haemmerle, G;Lass, A;Zechner, R
通讯作者：
Zechner, R
影响因子：
29
作者：
Biddinger, Sudha B.;Hernandez-Ono, Antonio;Kahn, C. Ronald
通讯作者：
Kahn, C. Ronald
DOI：
10.1016/0300-9629(82)90189-x
发表时间：
1982-01-01
影响因子：
2.3
作者：
GRIGGIO, MA
通讯作者：
GRIGGIO, MA
DOI：
10.1073/pnas.97.2.787
发表时间：
2000-01-18
影响因子：
11.1
作者：
Osuga, J;Ishibashi, S;Yamada, N
通讯作者：
Yamada, N