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dc.contributor.authorChen, Zhiminen_US
dc.contributor.authorWang, Guo-Xiaoen_US
dc.contributor.authorJung, Dae Youngen_US
dc.contributor.authorHa, Hyekyungen_US
dc.contributor.authorAltamimi, Tariqen_US
dc.contributor.authorZhao, Xu-Yunen_US
dc.contributor.authorGuo, Liangen_US
dc.contributor.authorZhang, Pengen_US
dc.contributor.authorHu, Chun-Ruien_US
dc.contributor.authorCheng, Ji-Xinen_US
dc.contributor.authorMa, Sara L.en_US
dc.contributor.authorLopaschuk, Gary D.en_US
dc.contributor.authorKim, Jason K.en_US
dc.contributor.authorLin, Jiandie D.en_US
dc.coverage.spatialGermanyen_US
dc.date2017-03-27
dc.date.accessioned2017-11-13T20:22:24Z
dc.date.available2017-11-13T20:22:24Z
dc.date.issued2017-08
dc.identifierhttps://www.ncbi.nlm.nih.gov/pubmed/28752050
dc.identifier.citationZhimin Chen, Guo-Xiao Wang, Sara L. Ma, Dae Young Jung, Hyekyung Ha, Tariq Altamimi, Xu-Yun Zhao, Liang Guo, Peng Zhang, Chun-Rui Hu, Ji-Xin Cheng, Gary D. Lopaschuk, Jason K. Kim, Jiandie D. Lin. 2017. "Nrg4 promotes fuel oxidation and a healthy adipokine profile to ameliorate diet-induced metabolic disorders.." Molecular Metabolism, v. 6, Issue 8, pp. 863 - 872.
dc.identifier.issn2212-8778
dc.identifier.urihttps://hdl.handle.net/2144/25233
dc.description.abstractOBJECTIVE: Brown and white adipose tissue exerts pleiotropic effects on systemic energy metabolism in part by releasing endocrine factors. Neuregulin 4 (Nrg4) was recently identified as a brown fat-enriched secreted factor that ameliorates diet-induced metabolic disorders, including insulin resistance and hepatic steatosis. However, the physiological mechanisms through which Nrg4 regulates energy balance and glucose and lipid metabolism remain incompletely understood. The aims of the current study were: i) to investigate the regulation of adipose Nrg4 expression during obesity and the physiological signals involved, ii) to elucidate the mechanisms underlying Nrg4 regulation of energy balance and glucose and lipid metabolism, and iii) to explore whether Nrg4 regulates adipose tissue secretome gene expression and adipokine secretion. METHODS: We examined the correlation of adipose Nrg4 expression with obesity in a cohort of diet-induced obese mice and investigated the upstream signals that regulate Nrg4 expression. We performed metabolic cage and hyperinsulinemic-euglycemic clamp studies in Nrg4 transgenic mice to dissect the metabolic pathways regulated by Nrg4. We investigated how Nrg4 regulates hepatic lipid metabolism in the fasting state and explored the effects of Nrg4 on adipose tissue gene expression, particularly those encoding secreted factors. RESULTS: Adipose Nrg4 expression is inversely correlated with adiposity and regulated by pro-inflammatory and anti-inflammatory signaling. Transgenic expression of Nrg4 increases energy expenditure and augments whole body glucose metabolism. Nrg4 protects mice from diet-induced hepatic steatosis in part through activation of hepatic fatty acid oxidation and ketogenesis. Finally, Nrg4 promotes a healthy adipokine profile during obesity. CONCLUSIONS: Nrg4 exerts pleiotropic beneficial effects on energy balance and glucose and lipid metabolism to ameliorate obesity-associated metabolic disorders. Biologic therapeutics based on Nrg4 may improve both type 2 diabetes and non-alcoholic fatty liver disease (NAFLD) in patients.en_US
dc.description.sponsorshipR21 AG055379 - NIA NIH HHS; K99 DK106664 - NIDDK NIH HHS; P30 DK089503 - NIDDK NIH HHS; R01 DK102456 - NIDDK NIH HHS; U2C DK093000 - NIDDK NIH HHS; P30 DK020572 - NIDDK NIH HHSen_US
dc.format.extentp. 863-872en_US
dc.languageeng
dc.language.isoen_US
dc.publisherElsevieren_US
dc.relation.ispartofMolecular Metabolism
dc.rightsAttribution 4.0 Internationalen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectAdipokineen_US
dc.subjectDiabetesen_US
dc.subjectBrown faten_US
dc.subjectGPR120, G-protein coupled receptor 120en_US
dc.subjecteWAT, epididymal WATen_US
dc.subjectScience & technologyen_US
dc.subjectLife Sciences & biomedicineen_US
dc.subjectEndocrinology & metabolismen_US
dc.subjectAdipose tissue dysfunctionen_US
dc.subjectFibroblast growth factorsen_US
dc.subjectInsulin resistanceen_US
dc.subjectSkeletal muscleen_US
dc.subjectInduced obesityen_US
dc.subjectFatty acidsen_US
dc.subjectReceptoren_US
dc.subjectBAT, brown adipose tissueen_US
dc.subjectBMPs, bone morphogenetic proteinsen_US
dc.subjectFGF21, fibroblast growth factor 21en_US
dc.subjectHFD, high fat dieten_US
dc.subjectCoA, co-enzyme Aen_US
dc.subjectIL-6, interleukin-6en_US
dc.subjectKO, knockouten_US
dc.subjectNALFD, non-alcoholic fatty liver diseaseen_US
dc.subjectNrg4, neuregulin 4en_US
dc.subjectTAG, triglycerideen_US
dc.subjectTNFα, tumor necrosis factor αen_US
dc.subjectTg, transgenicen_US
dc.subjectUCP-1, uncoupling protein 1en_US
dc.subjectVEGFα, vascular endothelial growth factor αen_US
dc.subjectWAT, white adipose tissueen_US
dc.subjectWT, wild typeen_US
dc.titleNrg4 promotes fuel oxidation and a healthy adipokine profile to ameliorate diet-induced metabolic disordersen_US
dc.typeArticleen_US
dc.identifier.doi10.1016/j.molmet.2017.03.016
pubs.elements-sourcepubmeden_US
pubs.notesEmbargo: Not knownen_US
pubs.organisational-groupBoston Universityen_US
pubs.organisational-groupBoston University, College of Engineeringen_US
pubs.organisational-groupBoston University, College of Engineering, Department of Electrical & Computer Engineeringen_US
pubs.publication-statusPublished onlineen_US
dc.identifier.orcid0000-0002-5607-6683 (Cheng, Ji-Xin)


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Attribution 4.0 International
Except where otherwise noted, this item's license is described as Attribution 4.0 International