title: Uncoupling of inflammation and insulin resistance by NF-kappaB in transgenic mice through elevated energy expenditure.
abstract: To study the metabolic activity of NF-kappaB, we investigated phenotypes of two different mouse models with elevated NF-kappaB activities. The transcriptional activity of NF-kappaB is enhanced either by overexpression of NF-kappaB p65 (RelA) in aP2-p65 mice or inactivation of NF-kappaB p50 (NF-kappaB1) through gene knock-out. In these models, energy expenditure was elevated in day and night time without a change in locomotion. The mice were resistant to adulthood obesity and diet-induced obesity without reduction in food intake. The adipose tissue growth and adipogenesis were inhibited by the elevated NF-kappaB activity. Peroxisome proliferator-activator receptor gamma expression was reduced by NF-kappaB at the transcriptional level. The two models exhibited elevated inflammatory cytokines (tumor necrosis factor-alpha and interleukin-6) in adipose tissue and serum. However, insulin sensitivity was not reduced by the inflammation in the mice on a chow diet. On a high fat diet, the mice were protected from insulin resistance. The glucose infusion rate was increased more than 30% in the hyperinsulinemic-euglycemic clamp test. Our data suggest that the transcription factor NF-kappaB promotes energy expenditure and inhibits adipose tissue growth. The two effects lead to prevention of adulthood obesity and dietary obesity. The energy expenditure may lead to disassociation of inflammation with insulin resistance. The study indicates that inflammation may prevent insulin resistance by eliminating lipid accumulation.
authors.affiliation: Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, Louisiana 70808, USA.
authors.forename: Tianyi
authors.initials: T
authors.lastname: Tang
authors.forename: Jin
authors.initials: J
authors.lastname: Zhang
authors.forename: Jun
authors.initials: J
authors.lastname: Yin
authors.forename: Jaroslaw
authors.initials: J
authors.lastname: Staszkiewicz
authors.forename: Barbara
authors.initials: B
authors.lastname: Gawronska-Kozak
authors.forename: Dae Young
authors.initials: DY
authors.lastname: Jung
authors.forename: Hwi Jin
authors.initials: HJ
authors.lastname: Ko
authors.forename: Helena
authors.initials: H
authors.lastname: Ong
authors.forename: Jason K
authors.initials: JK
authors.lastname: Kim
authors.forename: Randy
authors.initials: R
authors.lastname: Mynatt
authors.forename: Roy J
authors.initials: RJ
authors.lastname: Martin
authors.forename: Michael
authors.initials: M
authors.lastname: Keenan
authors.forename: Zhanguo
authors.initials: Z
authors.lastname: Gao
authors.forename: Jianping
authors.initials: J
authors.lastname: Ye
mesh_terms: D050156:Adipogenesis / Q000235:genetics / Q000502:physiology; D052436:Adipose Tissue, White / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D001823:Body Composition / Q000235:genetics / Q000502:physiology; D001831:Body Temperature; D001835:Body Weight / Q000235:genetics / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D004435:Eating / Q000235:genetics / Q000502:physiology; D024202:Electrophoretic Mobility Shift Assay; D004734:Energy Metabolism / Q000235:genetics / Q000502:physiology*; D050556:Fatty Acid-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005951:Glucose Tolerance Test; D007249:Inflammation / Q000235:genetics / Q000378:metabolism; D007333:Insulin Resistance / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000235:genetics / Q000502:physiology*; D009765:Obesity / Q000139:chemically induced / Q000235:genetics; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C493411:Fabp4 protein, mouse; D050556:Fatty Acid-Binding Proteins; D016328:NF-kappa B; D047495:PPAR gamma