title: Key Role of STAT4 Deficiency in the Hematopoietic Compartment in Insulin Resistance and Adipose Tissue Inflammation.
abstract: Visceral adipose tissue (AT) inflammation is linked to the complications of obesity, including insulin resistance (IR) and type 2 diabetes. Recent data from our lab showed that germline deficiency in STAT4 reduces inflammation and improves IR in obese mice. The objective of this study was to determine the contribution of selective STAT4 deficiency in subsets of hematopoietic cells to IR and AT inflammation. To determine the contribution of hematopoietic lineage, we sublethally irradiatedStat4-/-C57Bl6mice and reconstituted them with bone marrow cells (BMC) fromStat4+/+C57Bl6congenic donors. We also established the contribution of selective STAT4 deficiency in CD4+ or CD8+ T cells using adoptive transfer inRag1-/-mice. All mice received a HFD for 15 weeks (n= 7-12 mice/group). BMC that expressed STAT4 induced increases in glucose intolerance and IR compared to STAT4-deficient cells. Also, AT inflammation was increased and the numbers of CD8+ cells infiltrating AT were higher in mice with STAT4 expressing BMC. Studies inRag1-/-mice further confirmed the prominent role of CD8+ cells expressing STAT4 in insulin resistance and AT and islet inflammation. Collectively our results show specific and dominant contribution of STAT4 in the hematopoietic compartment to metabolic health and inflammation in diet-induced obesity.
authors.affiliation: Department of Physiological Sciences, Strelitz Diabetes Center, Eastern Virginia Medical School, Norfolk, VA, USA.
authors.forename: Anca D
authors.identifier: 0000-0003-3322-4214
authors.initials: AD
authors.lastname: Dobrian
authors.affiliation: Department of Internal Medicine, Strelitz Diabetes Center, Eastern Virginia Medical School, Norfolk, VA, USA.
authors.forename: Kaiwen
authors.initials: K
authors.lastname: Ma
authors.affiliation: Department of Internal Medicine, Strelitz Diabetes Center, Eastern Virginia Medical School, Norfolk, VA, USA.
authors.forename: Lindsey M
authors.initials: LM
authors.lastname: Glenn
authors.affiliation: Department of Physiological Sciences, Strelitz Diabetes Center, Eastern Virginia Medical School, Norfolk, VA, USA.
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Hatcher
authors.affiliation: Department of Physiological Sciences, Strelitz Diabetes Center, Eastern Virginia Medical School, Norfolk, VA, USA.
authors.forename: Bronson A
authors.initials: BA
authors.lastname: Haynes
authors.affiliation: Department of Physiological Sciences, Strelitz Diabetes Center, Eastern Virginia Medical School, Norfolk, VA, USA.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Lehrer
authors.affiliation: Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Mark H
authors.initials: MH
authors.lastname: Kaplan
authors.affiliation: Department of Internal Medicine, Strelitz Diabetes Center, Eastern Virginia Medical School, Norfolk, VA, USA.
authors.forename: Jerry L
authors.identifier: 0000-0002-4200-6991
authors.initials: JL
authors.lastname: Nadler
mesh_terms: D017667:Adipocytes / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D005434:Flow Cytometry; D006410:Hematopoiesis / Q000235:genetics / Q000502:physiology; D007249:Inflammation / Q000235:genetics / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000235:genetics / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D060888:Real-Time Polymerase Chain Reaction; D050797:STAT4 Transcription Factor / Q000235:genetics / Q000378:metabolism*
chemical_list: D007328:Insulin; D050797:STAT4 Transcription Factor; C494091:Stat4 protein, mouse