Deletion of Nhlh2 Results in a Defective Torpor Response and Reduced Beta Adrenergic Receptor Expression in Adipose Tissue

dc.contributor.authorWankhade, U. D.en
dc.contributor.authorVella, K. R.en
dc.contributor.authorFox, D. L.en
dc.contributor.authorGood, Deborah J.en
dc.contributor.departmentHuman Nutrition, Foods, and Exerciseen
dc.date.accessioned2017-02-08T13:15:06Zen
dc.date.available2017-02-08T13:15:06Zen
dc.date.issued2010-08-23en
dc.description.abstractBackground: Mice with a targeted deletion of the basic helix-loop-helix transcription factor, Nescient Helix-Loop-Helix 2 (Nhlh2), display adult-onset obesity with significant increases in their fat depots, abnormal responses to cold exposure, and reduced spontaneous physical activity levels. These phenotypes, accompanied by the hypothalamic expression of Nhlh2, make the Nhlh2 knockout (N2KO) mouse a useful model to study the role of central nervous system (CNS) control on peripheral tissue such as adipose tissue. Methodology: Differences in body temperature and serum analysis of leptin were performed in fasted and ad lib fed wildtype (WT) and N2KO mice. Histological analysis of white (WAT) and brown adipose tissue (BAT) was performed. Gene and protein level expression of inflammatory and metabolic markers were compared between the two genotypes. Principal Findings: We report significant differences in serum leptin levels and body temperature in N2KO mice compared with WT mice exposed to a 24-hour fast, suggestive of a defect in both white (WAT) and brown adipose tissue (BAT) function. As compared to WT mice, N2KO mice showed increased serum IL-6 protein and WAT IL-6 mRNA levels. This was accompanied by slight elevations of mRNA for several macrophage markers, including expression of macrophage specific protein F4/80 in adipose, suggestive of macrophage infiltration of WAT in the mutant animals. The mRNAs for β3-adrenergic receptors (β3-AR), β2-AR and uncoupling proteins were significantly reduced in WAT and BAT from N2KO mice compared with WT mice. Conclusions: These studies implicate Nhlh2 in the central control of WAT and BAT function, with lack of Nhlh2 leading to adipose inflammation and altered gene expression, impaired leptin response to fasting, all suggestive of a deficient torpor response in mutant animals.en
dc.description.versionPublished versionen
dc.format.extent9 pagesen
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0012324en
dc.identifier.issn1932-6203en
dc.identifier.issue8en
dc.identifier.urihttp://hdl.handle.net/10919/74962en
dc.identifier.volume5en
dc.language.isoenen
dc.publisherPLOSen
dc.relation.urihttp://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000281153500010&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=930d57c9ac61a043676db62af60056c1en
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectbeta-3-adrenergic receptoren
dc.subjectcold-exposureen
dc.subjectadult humansen
dc.subjectmolecular characterizationen
dc.subjectgene-expressionen
dc.subjectobese geneen
dc.subjectbrownen
dc.subjectmiceen
dc.subjecttranscriptionen
dc.subjectfaten
dc.titleDeletion of Nhlh2 Results in a Defective Torpor Response and Reduced Beta Adrenergic Receptor Expression in Adipose Tissueen
dc.title.serialPLOS ONEen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciencesen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciences/CALS T&R Facultyen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciences/Human Nutrition, Foods, & Exerciseen
pubs.organisational-group/Virginia Tech/All T&R Facultyen
pubs.organisational-group/Virginia Tech/Faculty of Health Sciencesen

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