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dc.contributor.authorDiStefano, Marina
dc.contributor.authorRoth Flach, Rachel J.
dc.contributor.authorSenol-Cosar, Ozlem
dc.contributor.authorDanai, Laura V.
dc.contributor.authorVirbasius, Joseph V.
dc.contributor.authorNicoloro, Sarah M.
dc.contributor.authorStraubhaar, Juerg R.
dc.contributor.authorDagdeviren, Sezin
dc.contributor.authorWabitsch, Martin
dc.contributor.authorGupta, Olga T.
dc.contributor.authorKim, Jason K.
dc.contributor.authorCzech, Michael P.
dc.date2022-08-11T08:09:46.000
dc.date.accessioned2022-08-23T16:42:41Z
dc.date.available2022-08-23T16:42:41Z
dc.date.issued2016-09-28
dc.date.submitted2017-01-09
dc.identifier.citationMol Metab. 2016 Sep 28;5(12):1149-1161. eCollection 2016 Dec. <a href="http://dx.doi.org/10.1016/j.molmet.2016.09.009">Link to article on publisher's site</a>
dc.identifier.issn2212-8778 (Linking)
dc.identifier.doi10.1016/j.molmet.2016.09.009
dc.identifier.pmid27900258
dc.identifier.urihttp://hdl.handle.net/20.500.14038/40144
dc.description.abstractOBJECTIVE: Adipose tissue relies on lipid droplet (LD) proteins in its role as a lipid-storing endocrine organ that controls whole body metabolism. Hypoxia-inducible Gene 2 (Hig2) is a recently identified LD-associated protein in hepatocytes that promotes hepatic lipid storage, but its role in the adipocyte had not been investigated. Here we tested the hypothesis that Hig2 localization to LDs in adipocytes promotes adipose tissue lipid deposition and systemic glucose homeostasis. METHOD: White and brown adipocyte-deficient (Hig2fl/fl x Adiponection cre+) and selective brown/beige adipocyte-deficient (Hig2fl/fl x Ucp1 cre+) mice were generated to investigate the role of Hig2 in adipose depots. Additionally, we used multiple housing temperatures to investigate the role of active brown/beige adipocytes in this process. RESULTS: Hig2 localized to LDs in SGBS cells, a human adipocyte cell strain. Mice with adipocyte-specific Hig2 deficiency in all adipose depots demonstrated reduced visceral adipose tissue weight and increased glucose tolerance. This metabolic effect could be attributed to brown/beige adipocyte-specific Hig2 deficiency since Hig2fl/fl x Ucp1 cre+ mice displayed the same phenotype. Furthermore, when adipocyte-deficient Hig2 mice were moved to thermoneutral conditions in which non-shivering thermogenesis is deactivated, these improvements were abrogated and glucose intolerance ensued. Adipocyte-specific Hig2 deficient animals displayed no detectable changes in adipocyte lipolysis or energy expenditure, suggesting that Hig2 may not mediate these metabolic effects by restraining lipolysis in adipocytes. CONCLUSIONS: We conclude that Hig2 localizes to LDs in adipocytes, promoting adipose tissue lipid deposition and that its selective deficiency in active brown/beige adipose tissue mediates improved glucose tolerance at 23 degrees C. Reversal of this phenotype at thermoneutrality in the absence of detectable changes in energy expenditure, adipose mass, or liver triglyceride suggests that Hig2 deficiency triggers a deleterious endocrine or neuroendocrine pathway emanating from brown/beige fat cells.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=27900258&dopt=Abstract">Link to Article in PubMed</a>
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectAdipocyte
dc.subjectBAT
dc.subjectbrown adipose tissue
dc.subjectFFA
dc.subjectfree fatty acid
dc.subjectGTT
dc.subjectglucose tolerance test
dc.subjectHFD
dc.subjecthigh fat diet
dc.subjectHig2
dc.subjectHypoxia-inducible gene 2
dc.subjectHypoxia-inducible gene 2 (Hig2)
dc.subjectITT
dc.subjectinsulin tolerance test
dc.subjectLD
dc.subjectlipid droplet
dc.subjectLipid droplet
dc.subjectLipolysis
dc.subjectNEFA
dc.subjectnon-esterified fatty acid
dc.subjectObesity
dc.subjectRER
dc.subjectrespiratory exchange ratio
dc.subjectSGBS
dc.subjectSimpson-Golabi-Behmel syndrome
dc.subjectSVF
dc.subjectstromal vascular fraction
dc.subjectTG
dc.subjecttriglyceride
dc.subjectUcp1
dc.subjectuncoupling protein 1
dc.subjectWAT
dc.subjectwhite adipose tissue
dc.subjecteWAT
dc.subjectepididymal white adipose tissue
dc.subjectiWAT
dc.subjectinguinal white adipose tissue
dc.subjectCell Biology
dc.subjectCellular and Molecular Physiology
dc.subjectEndocrinology
dc.subjectMolecular Biology
dc.titleAdipocyte-specific Hypoxia-inducible gene 2 promotes fat deposition and diet-induced insulin resistance
dc.typeJournal Article
dc.source.journaltitleMolecular metabolism
dc.source.volume5
dc.source.issue12
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=3949&amp;context=oapubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/2944
dc.identifier.contextkey9532598
refterms.dateFOA2022-08-23T16:42:41Z
html.description.abstract<p>OBJECTIVE: Adipose tissue relies on lipid droplet (LD) proteins in its role as a lipid-storing endocrine organ that controls whole body metabolism. Hypoxia-inducible Gene 2 (Hig2) is a recently identified LD-associated protein in hepatocytes that promotes hepatic lipid storage, but its role in the adipocyte had not been investigated. Here we tested the hypothesis that Hig2 localization to LDs in adipocytes promotes adipose tissue lipid deposition and systemic glucose homeostasis.</p> <p>METHOD: White and brown adipocyte-deficient (Hig2fl/fl x Adiponection cre+) and selective brown/beige adipocyte-deficient (Hig2fl/fl x Ucp1 cre+) mice were generated to investigate the role of Hig2 in adipose depots. Additionally, we used multiple housing temperatures to investigate the role of active brown/beige adipocytes in this process.</p> <p>RESULTS: Hig2 localized to LDs in SGBS cells, a human adipocyte cell strain. Mice with adipocyte-specific Hig2 deficiency in all adipose depots demonstrated reduced visceral adipose tissue weight and increased glucose tolerance. This metabolic effect could be attributed to brown/beige adipocyte-specific Hig2 deficiency since Hig2fl/fl x Ucp1 cre+ mice displayed the same phenotype. Furthermore, when adipocyte-deficient Hig2 mice were moved to thermoneutral conditions in which non-shivering thermogenesis is deactivated, these improvements were abrogated and glucose intolerance ensued. Adipocyte-specific Hig2 deficient animals displayed no detectable changes in adipocyte lipolysis or energy expenditure, suggesting that Hig2 may not mediate these metabolic effects by restraining lipolysis in adipocytes.</p> <p>CONCLUSIONS: We conclude that Hig2 localizes to LDs in adipocytes, promoting adipose tissue lipid deposition and that its selective deficiency in active brown/beige adipose tissue mediates improved glucose tolerance at 23 degrees C. Reversal of this phenotype at thermoneutrality in the absence of detectable changes in energy expenditure, adipose mass, or liver triglyceride suggests that Hig2 deficiency triggers a deleterious endocrine or neuroendocrine pathway emanating from brown/beige fat cells.</p>
dc.identifier.submissionpathoapubs/2944
dc.contributor.departmentUMass Metabolic Network
dc.contributor.departmentDepartment of Medicine, Division of Endocrinology, Metabolism and Diabetes
dc.contributor.departmentProgram in Molecular Medicine
dc.source.pages1149-1161


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