Lipocalin-2 Deficiency Impairs Thermogenesis and Potentiates Diet-Induced Insulin Resistance in Mice.
Guo, Hong 1; Jin, Daozhong 1; Zhang, Yuanyuan 1; Wright, Wendy 2; Bazuine, Merlijn 3; Brockman, David A. 1; Bernlohr, David A. 2; Chen, Xiaoli 1,
[Article] Diabetes. 59(6):1376-1385, June 2010.

(Format: HTML, PDF)

OBJECTIVE: 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.

RESEARCH DESIGN AND METHODS: 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.

RESULTS: 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.

CONCLUSIONS: LCN2 has a novel role in adaptive thermoregulation and diet-induced insulin resistance.

(C) 2010 by the American Diabetes Association, Inc.