Article: Major urinary protein-1 increases energy expenditure and improves glucose intolerance through enhancing mitochondrial function in skeletal muscle of diabetic mice

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TitleMajor urinary protein-1 increases energy expenditure and improves glucose intolerance through enhancing mitochondrial function in skeletal muscle of diabetic mice
AuthorsHui, X1
Zhu, W2
Wang, Y2
Lam, KSL2
Zhang, J2
Wu, D3
Kraegen, EW4
Li, Y1
Xu, A2
Issue Date2009
PublisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/
CitationJournal Of Biological Chemistry, 2009, v. 284 n. 21, p. 14050-14057 [How to Cite?]
DOI: http://dx.doi.org/10.1074/jbc.M109.001107
AbstractMajor urinary protein-1 (MUP-1) is a low molecular weight secreted protein produced predominantly from the liver. Structurally it belongs to the lipocalin family, which carries small hydrophobic ligands such as pheromones. However, the physiological functions of MUP-1 remain poorly understood. Here we provide evidence demonstrating that MUP-1 is an important player in regulating energy expenditure and metabolism in mice. Both microarray and real-time PCR analysis demonstrated that the MUP-1 mRNA abundance in the liver of db/db obese mice was reduced by ∼30-fold compared with their lean littermates, whereas this change was partially reversed by treatment with the insulin-sensitizing drug rosiglitazone. In both dietary and genetic obese mice, the circulating concentrations of MUP-1 were markedly decreased compared with the lean controls. Chronic elevation of circulating MUP-1 in db/db mice, using an osmotic pump-based protein delivery system, increased energy expenditure and locomotor activity, raised core body temperature, and decreased glucose intolerance as well as insulin resistance. At the molecular level, MUP-1-mediated improvement in metabolic profiles was accompanied by increased expression of genes involved in mitochondrial biogenesis, elevated mitochondrial oxidative capacity, decreased triglyceride accumulation, and enhanced insulin-evoked Akt signaling in skeletal muscle but not in liver. Altogether, these findings raise the possibility that MUP-1 deficiency might contribute to the metabolic dysregulation in obese/diabetic mice, and suggest that the beneficial metabolic effects of MUP-1 are attributed in part to its ability in increasing mitochondrial function in skeletal muscle. © 2009 by The American Society for Biochemistry and Molecular Biology, Inc.
ISSN0021-9258
2011 Impact Factor: 4.773
2011 SCImago Journal Rankings: 0.793
DOIhttp://dx.doi.org/10.1074/jbc.M109.001107
ReferencesReferences in Scopus
DC Field
Value
dc.contributor.authorHui, X
dc.contributor.authorZhu, W
dc.contributor.authorWang, Y
dc.contributor.authorLam, KSL
dc.contributor.authorZhang, J
dc.contributor.authorWu, D
dc.contributor.authorKraegen, EW
dc.contributor.authorLi, Y
dc.contributor.authorXu, A
dc.date.accessioned2012-09-05T05:29:15Z
dc.date.available2012-09-05T05:29:15Z
dc.date.issued2009
dc.description.abstractMajor urinary protein-1 (MUP-1) is a low molecular weight secreted protein produced predominantly from the liver. Structurally it belongs to the lipocalin family, which carries small hydrophobic ligands such as pheromones. However, the physiological functions of MUP-1 remain poorly understood. Here we provide evidence demonstrating that MUP-1 is an important player in regulating energy expenditure and metabolism in mice. Both microarray and real-time PCR analysis demonstrated that the MUP-1 mRNA abundance in the liver of db/db obese mice was reduced by ∼30-fold compared with their lean littermates, whereas this change was partially reversed by treatment with the insulin-sensitizing drug rosiglitazone. In both dietary and genetic obese mice, the circulating concentrations of MUP-1 were markedly decreased compared with the lean controls. Chronic elevation of circulating MUP-1 in db/db mice, using an osmotic pump-based protein delivery system, increased energy expenditure and locomotor activity, raised core body temperature, and decreased glucose intolerance as well as insulin resistance. At the molecular level, MUP-1-mediated improvement in metabolic profiles was accompanied by increased expression of genes involved in mitochondrial biogenesis, elevated mitochondrial oxidative capacity, decreased triglyceride accumulation, and enhanced insulin-evoked Akt signaling in skeletal muscle but not in liver. Altogether, these findings raise the possibility that MUP-1 deficiency might contribute to the metabolic dysregulation in obese/diabetic mice, and suggest that the beneficial metabolic effects of MUP-1 are attributed in part to its ability in increasing mitochondrial function in skeletal muscle. © 2009 by The American Society for Biochemistry and Molecular Biology, Inc.
dc.description.natureLink_to_subscribed_fulltext
dc.identifier.citationJournal Of Biological Chemistry, 2009, v. 284 n. 21, p. 14050-14057 [How to Cite?]
DOI: http://dx.doi.org/10.1074/jbc.M109.001107
dc.identifier.citeulike6416774
dc.identifier.doihttp://dx.doi.org/10.1074/jbc.M109.001107
dc.identifier.epage14057
dc.identifier.hkuros157898
dc.identifier.issn0021-9258
2011 Impact Factor: 4.773
2011 SCImago Journal Rankings: 0.793
dc.identifier.issue21
dc.identifier.pmid19336396
dc.identifier.scopuseid_2-s2.0-67649774119
dc.identifier.spage14050
dc.identifier.urihttp://hdl.handle.net/10722/163258
dc.identifier.volume284
dc.languageeng
dc.publisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/
dc.publisher.placeUnited States
dc.relation.ispartofJournal of Biological Chemistry
dc.relation.referencesReferences in Scopus
dc.rightsJournal of Biological Chemistry. Copyright © American Society for Biochemistry and Molecular Biology, Inc.
dc.subject.meshAnimals
dc.subject.meshDiabetes Mellitus, Experimental - Complications - Enzymology - Physiopathology
dc.subject.meshDietary Fats - Administration & Dosage - Pharmacology
dc.subject.meshEnergy Metabolism - Drug Effects
dc.subject.meshFeeding Behavior - Drug Effects
dc.subject.meshGlucose Intolerance - Complications - Physiopathology
dc.subject.meshInsulin - Pharmacology
dc.subject.meshInsulin Resistance
dc.subject.meshLipid Metabolism - Drug Effects
dc.subject.meshLiver - Drug Effects - Metabolism - Physiopathology
dc.subject.meshMice
dc.subject.meshMice, Inbred C57bl
dc.subject.meshMice, Obese
dc.subject.meshMitochondria - Drug Effects - Metabolism
dc.subject.meshMotor Activity - Drug Effects
dc.subject.meshMuscle, Skeletal - Drug Effects - Enzymology - Physiopathology
dc.subject.meshProteins - Metabolism
dc.subject.meshProto-Oncogene Proteins C-Akt - Metabolism
dc.subject.meshRecombinant Proteins - Administration & Dosage - Pharmacology
dc.subject.meshSignal Transduction - Drug Effects
dc.subject.meshThiazolidinediones - Pharmacology
dc.subject.meshUp-Regulation - Drug Effects
dc.titleMajor urinary protein-1 increases energy expenditure and improves glucose intolerance through enhancing mitochondrial function in skeletal muscle of diabetic mice
dc.typeArticle
Author Affiliations
  1. Graduate University of Chinese Academy of Sciences
  2. The University of Hong Kong
  3. Chinese Academy of Sciences
  4. University of New South Wales