title: Transcriptome profiling reveals divergent expression shifts in brown and white adipose tissue from long-lived GHRKO mice.
abstract: Mice lacking the growth hormone receptor (GHRKO) exhibit improved lifespan and healthspan due to loss of growth hormone signaling. Both the distribution and activity of brown and white adipose tissue (BAT and WAT) are altered in GHRKO mice, but the contribution of each tissue to age-related phenotypes has remained unclear. We therefore used whole-genome microarrays to evaluate transcriptional differences in BAT and WAT depots between GHRKO and normal littermates at six months of age. Our findings reveal a unique BAT transcriptome as well as distinctive responses of BAT to Ghr ablation. BAT from GHRKO mice exhibited elevated expression of genes associated with mitochondria and metabolism, along with reduced expression of genes expressed by monocyte-derived cells (dendritic cells [DC] and macrophages). Largely the opposite was observed in WAT, with increased expression of DC-expressed genes and reduced expression of genes associated with metabolism, cellular respiration and the mitochondrial inner envelope. These findings demonstrate divergent response patterns of BAT and WAT to loss of GH signaling in GHRKO mice. These patterns suggest both BAT and WAT contribute in different ways to phenotypes in GHRKO mice, with Ghr ablation blunting inflammation in BAT as well as cellular metabolism and mitochondrial biogenesis in WAT.
authors.affiliation: Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, USA.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Stout
authors.affiliation: Department of Dermatology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: William R
authors.initials: WR
authors.lastname: Swindell
authors.affiliation: Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China.|College of Medicine, Burnett School of Biomedical Sciences, University of Central Florida, Orlando, FL, USA.
authors.forename: Xu
authors.initials: X
authors.lastname: Zhi
authors.affiliation: College of Medicine, Burnett School of Biomedical Sciences, University of Central Florida, Orlando, FL, USA.
authors.forename: Kyle
authors.initials: K
authors.lastname: Rohde
authors.affiliation: Edison Biotechnology Institute and Heritage College of Osteopathic Medicine, Ohio University, Athens, OH, USA.
authors.forename: Edward O
authors.initials: EO
authors.lastname: List
authors.affiliation: Edison Biotechnology Institute and Heritage College of Osteopathic Medicine, Ohio University, Athens, OH, USA.
authors.forename: Darlene E
authors.initials: DE
authors.lastname: Berryman
authors.affiliation: Edison Biotechnology Institute and Heritage College of Osteopathic Medicine, Ohio University, Athens, OH, USA.
authors.forename: John J
authors.initials: JJ
authors.lastname: Kopchick
authors.affiliation: Department of Oncological Endocrinology, Medical University of Lodz, Lodz, Poland.
authors.forename: Adam
authors.initials: A
authors.lastname: Gesing
authors.affiliation: Geriatrics Research Laboratory, Department of Internal Medicine, Southern Illinois University School of Medicine, Springfield, IL, USA.
authors.forename: Yimin
authors.initials: Y
authors.lastname: Fang
authors.affiliation: College of Medicine, Burnett School of Biomedical Sciences, University of Central Florida, Orlando, FL, USA.|Department of Head and Neck Surgery, The Greater Poland Cancer Centre, Poznan, Poland.
authors.forename: Michal M
authors.initials: MM
authors.lastname: Masternak
mesh_terms: D002001:Adipose Tissue, Brown / Q000378:metabolism*; D052436:Adipose Tissue, White / Q000378:metabolism*; D000465:Algorithms; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics*; D019295:Computational Biology; D003713:Dendritic Cells / Q000166:cytology; D020869:Gene Expression Profiling; D007249:Inflammation; D008264:Macrophages / Q000166:cytology; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000378:metabolism; D009000:Monocytes / Q000166:cytology; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D012313:RNA / Q000032:analysis; D014158:Transcription, Genetic; D059467:Transcriptome
chemical_list: D002352:Carrier Proteins; D012313:RNA; C051815:somatotropin-binding protein
keywords: Gerotarget section; brown adipose tissue; growth hormone; inflammation; metabolism; white adipose tissue