Oncotarget

Research Papers: Gerotarget (Focus on Aging):

Transcriptome profiling reveals divergent expression shifts in brown and white adipose tissue from long-lived GHRKO mice

Michael B. Stout, William R. Swindell, Xu Zhi, Kyle Rohde, Edward O. List, Darlene E. Berryman, John J. Kopchick, Adam Gesing, Yimin Fang and Michal M. Masternak _

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Oncotarget. 2015; 6:26702-26715. https://doi.org/10.18632/oncotarget.5760

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Abstract

Michael B. Stout1,*, William R. Swindell2,*, Xu Zhi3,4, Kyle Rohde4, Edward O. List5, Darlene E. Berryman5, John J. Kopchick5, Adam Gesing6, Yimin Fang7 and Michal M. Masternak4,8

1 Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, USA

2 Department of Dermatology, University of Michigan, Ann Arbor, MI, USA

3 Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China

4 College of Medicine, Burnett School of Biomedical Sciences, University of Central Florida, Orlando, FL, USA

5 Edison Biotechnology Institute and Heritage College of Osteopathic Medicine, Ohio University, Athens, OH, USA

6 Department of Oncological Endocrinology, Medical University of Lodz, Lodz, Poland

7 Geriatrics Research Laboratory, Department of Internal Medicine, Southern Illinois University School of Medicine, Springfield, IL, USA

8 Department of Head and Neck Surgery, The Greater Poland Cancer Centre, Poznan, Poland

* These authors have contributed equally to this work

Correspondence to:

Michal M. Masternak, email:

Michael B. Stout, email:

Keywords: brown adipose tissue, growth hormone, inflammation, metabolism, white adipose tissue, Gerotarget section

Received: August 09, 2015 Accepted: August 29, 2015 Published: September 21, 2015

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.


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