Tamoxifen reduces fat mass by boosting reactive oxygen species

Simple item page
dc.contributorVirginia Tech. Department of Human Nutrition, Foods, and Exerciseen
dc.contributor.authorLiu, Longhuaen
dc.contributor.authorZou, Pengen
dc.contributor.authorZheng, Louiseen
dc.contributor.authorLinarelli, Leah E.en
dc.contributor.authorAmarell, Sarah M.en
dc.contributor.authorPassaro, Austinen
dc.contributor.authorLiu, Dongminen
dc.contributor.authorCheng, Zhiyongen
dc.contributor.departmentHuman Nutrition, Foods, and Exerciseen
dc.contributor.editorFinazzi-Agrò, Alessandroen
dc.date.accessed2016-02-12en
dc.date.accessioned2016-02-16T08:03:30Zen
dc.date.available2016-02-16T08:03:30Zen
dc.date.issued2015-01-08en
dc.description.abstractAs the pandemic of obesity is growing, a variety of animal models have been generated to study the mechanisms underlying the increased adiposity and development of metabolic disorders. Tamoxifen (Tam) is widely used to activate Cre recombinase that spatiotemporally controls target gene expression and regulates adiposity in laboratory animals. However, a critical question remains as to whether Tam itself affects adiposity and possibly confounds the functional study of target genes in adipose tissue. Here we administered Tam to Cre-absent forkhead box O1 (FoxO1) floxed mice (f-FoxO1) and insulin receptor substrate Irs1/Irs2 double floxed mice (df-Irs) and found that Tam induced approximately 30% reduction (P<0.05) in fat mass with insignificant change in body weight. Mechanistically, Tam promoted reactive oxygen species (ROS) production, apoptosis and autophagy, which was associated with downregulation of adipogenic regulator peroxisome proliferator-activated receptor gamma and dedifferentiation of mature adipocytes. However, normalization of ROS potently suppressed Tam-induced apoptosis, autophagy and adipocyte dedifferentiation, suggesting that ROS may account, at least in part, for the changes. Importantly, Tam-induced ROS production and fat mass reduction lasted for 4-5 weeks in the f-FoxO1 and df-Irs mice. Our data suggest that Tam reduces fat mass via boosting ROS, thus making a recovery period crucial for posttreatment study.en
dc.description.sponsorshipVirginia Agricultural Experiment Stationen
dc.description.sponsorshipNational Institute of Food and Agriculture. Hatch Programen
dc.description.sponsorshipNational Institutes of Health. National Center for Complementary and Alternative Medicineen
dc.description.sponsorship1R01AT007077en
dc.description.sponsorshipVirginia Tech. Open Access Subvention Funden
dc.format.extent8 p.en
dc.format.mimetypeapplication/pdfen
dc.identifier.citationLiu, L., Zou, P., Zheng, L., Linarelli, L. E., Amarell, S., Passaro, A., . . . Cheng, Z. (2015). Tamoxifen reduces fat mass by boosting reactive oxygen species. Cell Death Dis, 6, e1586. doi:10.1038/cddis.2014.55en
dc.identifier.doihttps://doi.org/10.1038/cddis.2014.553en
dc.identifier.issn2041-4889en
dc.identifier.urihttp://hdl.handle.net/10919/64828en
dc.identifier.urlhttp://www.nature.com/cddis/journal/v6/n1/full/cddis2014553a.htmlen
dc.identifier.volume6en
dc.language.isoenen
dc.publisherNature Publishing Groupen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.holderMacmillan Publishers Limiteden
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.titleTamoxifen reduces fat mass by boosting reactive oxygen speciesen
dc.title.serialCell Death and Diseaseen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
Tamoxifen_reduces_fat_mass.pdf
Size:
1.38 MB
Format:
Adobe Portable Document Format
Description:
Download

Collections

Scholarly Works, Human Nutrition, Foods, and Exercise
Open Access Subvention Fund Articles