Show simple item record

dc.contributor.authorGuo, Chang-An
dc.contributor.authorKogan, Sophia
dc.contributor.authorAmano, Shinya U.
dc.contributor.authorWang, Mengxi
dc.contributor.authorDagdeviren, Sezin
dc.contributor.authorFriedline, Randall H.
dc.contributor.authorAouadi, Myriam
dc.contributor.authorKim, Jason K.
dc.contributor.authorCzech, Michael P.
dc.date2022-08-11T08:08:55.000
dc.date.accessioned2022-08-23T16:11:58Z
dc.date.available2022-08-23T16:11:58Z
dc.date.issued2013-03-12
dc.date.submitted2013-03-21
dc.identifier.citationAm J Physiol Endocrinol Metab. 2013 Mar 12. DOI 10.​1152/​ajpendo.​00514.​2012
dc.identifier.issn1522-1555
dc.identifier.doi10.​1152/​ajpendo.​00514.​2012
dc.identifier.pmid23482447
dc.identifier.urihttp://hdl.handle.net/20.500.14038/33293
dc.description.abstractThe pathophysiology of obesity and type 2 diabetes in rodents and humans is characterized by low-grade inflammation in adipose tissue and liver. The CD40 receptor and its ligand, CD40L, initiate immune cell signaling promoting inflammation, but conflicting data on CD40L null mice confound its role in obesity-associated insulin resistance. Here we demonstrate that CD40 receptor deficient mice on a high fat diet display the expected decrease in hepatic cytokine levels, but paradoxically exhibit liver steatosis, insulin resistance and glucose intolerance compared to their age-matched wild type controls. Hyperinsulinemic-euglycemic clamp studies also demonstrated insulin resistance in glucose utilization by the CD40 null mice compared to wild type mice. In contrast to liver, adipose tissue in CD40 deficient animals harbors elevated cytokine levels and infiltration of inflammatory cells, particularly macrophages and CD8+ effector T-cells. In addition, ex vivo explants of epididymal adipose tissue from CD40(-/-) mice display elevated basal and isoproterenol-stimulated lipolysis, suggesting a potential increase of lipid efflux from visceral fat to the liver. These findings reveal that, 1) CD40 null mice represent an unusual model of hepatic steatosis with reduced hepatic inflammation, and 2) CD40 unexpectedly functions in adipose tissue to attenuate its inflammation in obesity, thereby protecting against hepatic steatosis.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=23482447&dopt=Abstract">Link to article in PubMed</a>
dc.relation.urlhttp://dx.doi.org/10.1152/ajpendo.00514.2012
dc.subjectAntigens, CD40; Fatty Liver; Inflammation; Obesity; Adipose Tissue; Insulin Resistance
dc.subjectCellular and Molecular Physiology
dc.subjectEndocrinology
dc.titleCD40 Deficiency in Mice Exacerbates Obesity-induced Adipose Tissue Inflammation, Hepatic Steatosis and Insulin Resistance
dc.typeJournal Article
dc.source.journaltitleAmerican journal of physiology. Endocrinology and metabolism
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/gsbs_sp/1823
dc.identifier.contextkey3940438
html.description.abstract<p>The pathophysiology of obesity and type 2 diabetes in rodents and humans is characterized by low-grade inflammation in adipose tissue and liver. The CD40 receptor and its ligand, CD40L, initiate immune cell signaling promoting inflammation, but conflicting data on CD40L null mice confound its role in obesity-associated insulin resistance. Here we demonstrate that CD40 receptor deficient mice on a high fat diet display the expected decrease in hepatic cytokine levels, but paradoxically exhibit liver steatosis, insulin resistance and glucose intolerance compared to their age-matched wild type controls. Hyperinsulinemic-euglycemic clamp studies also demonstrated insulin resistance in glucose utilization by the CD40 null mice compared to wild type mice. In contrast to liver, adipose tissue in CD40 deficient animals harbors elevated cytokine levels and infiltration of inflammatory cells, particularly macrophages and CD8+ effector T-cells. In addition, ex vivo explants of epididymal adipose tissue from CD40(-/-) mice display elevated basal and isoproterenol-stimulated lipolysis, suggesting a potential increase of lipid efflux from visceral fat to the liver. These findings reveal that, 1) CD40 null mice represent an unusual model of hepatic steatosis with reduced hepatic inflammation, and 2) CD40 unexpectedly functions in adipose tissue to attenuate its inflammation in obesity, thereby protecting against hepatic steatosis.</p>
dc.identifier.submissionpathgsbs_sp/1823
dc.contributor.departmentProgram in Molecular Medicine
dc.contributor.studentChang-An Guo; Sophia Kogan; Shinya U. Amano; Mengxi Wang; Sezin Dagdeviren


This item appears in the following Collection(s)

Show simple item record