Obeticholic Acid Improves Adipose Morphometry and Inflammation and Reduces Steatosis in Dietary but not Metabolic Obesity in Mice

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dc.contributor.authorHaczeyni, Fahrettin
dc.contributor.authorPoekes, Laurence
dc.contributor.authorWang, Hans
dc.contributor.authorMridha, Auvro
dc.contributor.authorBarn, Vanessa
dc.contributor.authorHaigh, W. Geoffrey
dc.contributor.authorIoannou, George
dc.contributor.authorYeh, Matthew
dc.contributor.authorLeclercq, Isabelle A.
dc.contributor.authorTeoh, Narcissus
dc.contributor.authorFarrell, Geoffrey
dc.date.accessioned2021-08-23T00:46:08Z
dc.date.issued2017
dc.date.updated2020-11-23T10:53:38Z
dc.description.abstractObjective: Nonalcoholic steatohepatitis (NASH) is the outcome of interactions between overnutrition, energy metabolism, and adipose function. Obeticholic acid (OCA) improves steatosis in patients but for unknown reasons does not resolve NASH pathology. This study therefore investigated OCA effects in Wt mice, which develop obesity with atherogenic dietary feeding, and appetite-dysregulated, Alms1 mutant foz/foz mice fed the same diet, which develop metabolic obesity and diabetes. Methods: OCA (1 mg/kg) was administered orally to female foz/foz mice and Wt littermates from weaning until 28 weeks. Adipose indices, glucose tolerance, and fatty liver pathology were studied. Experiments were repeated with OCA 10 mg/kg. Results: OCA reduced body weight and hepatic lipids and improved glucose disposal only in Wt mice. OCA limited Wt adipose expansion, altered morphometry in favor of small adipocytes, enhanced expression of genes indicating adipose browning, and reduced crown-like structure number in visceral adipose tissue. foz/foz mice showed more crown-like structures in all compartments; OCA failed to alter adipose morphometry, browning, inflammation, or improve NASH severity, even at 10 mg/kg. Conclusions: OCA improved adipose indices, glucose tolerance, and steatosis in a milder metabolic phenotype but failed to improve these factors in morbidly obese diabetic mice. These results help explain OCA's limited efficacy to reverse human NASH.en_AU
dc.description.sponsorshipThis research was supported by Australia National Health and Medical Research Council’s (NHMRC) project grants: 585411, 1044288, and 102818.en_AU
dc.format.mimetypeapplication/pdfen_AU
dc.identifier.issn1930-7381en_AU
dc.identifier.urihttp://hdl.handle.net/1885/244967
dc.language.isoen_AUen_AU
dc.publisherObesity Societyen_AU
dc.relationhttp://purl.org/au-research/grants/nhmrc/585411en_AU
dc.relationhttp://purl.org/au-research/grants/nhmrc/1044288en_AU
dc.rights© 2016 The Obesity Societyen_AU
dc.sourceObesityen_AU
dc.titleObeticholic Acid Improves Adipose Morphometry and Inflammation and Reduces Steatosis in Dietary but not Metabolic Obesity in Miceen_AU
dc.typeJournal articleen_AU
local.bibliographicCitation.issue1en_AU
local.bibliographicCitation.lastpage165en_AU
local.bibliographicCitation.startpage155en_AU
local.contributor.affiliationHaczeyni, Fahrettin, College of Health and Medicine, ANUen_AU
local.contributor.affiliationPoekes, Laurence, Universite Catholique de Louvainen_AU
local.contributor.affiliationWang, Hans, College of Health and Medicine, ANUen_AU
local.contributor.affiliationMridha, Auvro, College of Health and Medicine, ANUen_AU
local.contributor.affiliationBarn, Vanessa, College of Health and Medicine, ANUen_AU
local.contributor.affiliationHaigh, W Geoffrey, University of Washingtonen_AU
local.contributor.affiliationIoannou, George, University of Washingtonen_AU
local.contributor.affiliationYeh, Matthew, University of Washingtonen_AU
local.contributor.affiliationLeclercq, Isabelle A, Catholic University of Louvainen_AU
local.contributor.affiliationTeoh, Narcissus, College of Health and Medicine, ANUen_AU
local.contributor.affiliationFarrell, Geoffrey, College of Health and Medicine, ANUen_AU
local.contributor.authoremailu4028700@anu.edu.auen_AU
local.contributor.authoruidHaczeyni, Fahrettin, u5076272en_AU
local.contributor.authoruidWang, Hans, u4232310en_AU
local.contributor.authoruidMridha, Auvro, u5219668en_AU
local.contributor.authoruidBarn, Vanessa, u4556662en_AU
local.contributor.authoruidTeoh, Narcissus, u4325419en_AU
local.contributor.authoruidFarrell, Geoffrey, u4028700en_AU
local.description.embargo2099-12-31
local.description.notesImported from ARIESen_AU
local.identifier.absfor111699 - Medical Physiology not elsewhere classifieden_AU
local.identifier.ariespublicationa383154xPUB6249en_AU
local.identifier.citationvolume25en_AU
local.identifier.doi10.1002/oby.21701en_AU
local.identifier.scopusID2-s2.0-84996521986
local.identifier.thomsonID000391215200019
local.identifier.uidSubmittedBya383154en_AU
local.publisher.urlhttps://www.wiley.com/en-gben_AU
local.type.statusPublished Versionen_AU

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