title: Lipocalin 2 expression and secretion is highly regulated by metabolic stress, cytokines, and nutrients in adipocytes.
abstract: Lipocalin 2 (Lcn2) has been recently characterized as a new adipokine having a role in innate immunity and energy metabolism. Nonetheless, the metabolic regulation of Lcn2 production in adipocytes has not been comprehensively studied. To better understand the Lcn2 biology, we investigated the regulation of Lcn2 expression in adipose tissue in response to metabolic stress in mice as well as the control of Lcn2 expression and secretion by cytokines and nutrients in 3T3-L1 adipocytes. Our results showed that the mRNA expression of Lcn2 was upregulated in white and brown adipose tissues as well as liver during fasting and cold stress in mice. Among pro-inflammatory cytokines TNFα, IL-1β, and IL-6, IL-1β showed most profound effect on Lcn2 expression and secretion in 3T3-L1 adipocytes. Insulin stimulated Lcn2 expression and secretion in a dose-dependent manner; this insulin effect was significantly abolished in the presence of low concentration of glucose. Moreover, insulin-stimulated Lcn2 expression and secretion was also attenuated when glucose was replaced by 3-O-methyl-d-glucose or by blocking NFκB pathway activation. Additionally, we showed that palmitate and oleate induced Lcn2 expression and secretion more significantly than EPA, while phytanic acid reduced Lcn2 production. Our results demonstrated that Lcn2 production in adipocytes is highly responsive to metabolic stress, cytokines, and nutrient signals, suggesting an important role of Lcn2 in adipocyte metabolism and inflammation.
authors.affiliation: Department of Food Science and Nutrition, University of Minnesota-Twin Cities, Saint Paul, Minnesota, United States of America.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota-Twin Cities, Minneapolis, Minnesota, United States of America.
authors.forename: Rocio
authors.initials: R
authors.lastname: Foncea
authors.affiliation: Department of Food Science and Nutrition, University of Minnesota-Twin Cities, Saint Paul, Minnesota, United States of America.
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Deis
authors.affiliation: Department of Food Science and Nutrition, University of Minnesota-Twin Cities, Saint Paul, Minnesota, United States of America.
authors.forename: Hong
authors.initials: H
authors.lastname: Guo
authors.affiliation: Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota-Twin Cities, Minneapolis, Minnesota, United States of America.
authors.forename: David A
authors.initials: DA
authors.lastname: Bernlohr
authors.affiliation: Department of Food Science and Nutrition, University of Minnesota-Twin Cities, Saint Paul, Minnesota, United States of America.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Chen
mesh_terms: D041721:3T3-L1 Cells; D000209:Acute-Phase Proteins / Q000235:genetics* / Q000378:metabolism*; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000273:Adipose Tissue / Q000166:cytology; D000818:Animals; D016207:Cytokines / Q000378:metabolism*; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D000071068:Lipocalin-2; D054834:Lipocalins / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D015513:Oncogene Proteins / Q000235:genetics* / Q000378:metabolism*; D018384:Oxidative Stress; D015398:Signal Transduction / Q000187:drug effects; D013312:Stress, Physiological
chemical_list: D000209:Acute-Phase Proteins; D016207:Cytokines; D007328:Insulin; D000071068:Lipocalin-2; D054834:Lipocalins; D016328:NF-kappa B; D015513:Oncogene Proteins; C071332:Lcn2 protein, mouse; D005947:Glucose