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Expression of GHR and Downstream Signaling Genes in Human Adipose Tissue-Relation to Obesity and Weight Change.

Journal article
Authors Camilla A M Glad
Per-Arne Svensson
Fredrik H Nystrom
Peter Jacobson
Lena M S Carlsson
Gudmundur Johannsson
Johanna C. Andersson-Assarsson
Published in The Journal of clinical endocrinology and metabolism
Volume 104
Issue 5
Pages 1459-1470
ISSN 1945-7197
Publication year 2019
Published at Institute of Medicine, Department of Internal Medicine and Clinical Nutrition
Institute of Health and Care Sciences
Institute of Medicine, Department of Molecular and Clinical Medicine
Pages 1459-1470
Language en
Links dx.doi.org/10.1210/jc.2018-01036
www.ncbi.nlm.nih.gov/entrez/query.f...
Subject categories Cell and Molecular Biology, Endocrinology

Abstract

GH is a strong regulator of metabolism. In obesity, both GH secretion and adipose tissue GHR gene expression are decreased. More detailed information on the regulation of GHR, STAT3/5, and downstream-regulated genes in human adipose tissue during diet-induced weight loss and weight gain is lacking.The aim of the present study was to investigate the gene expression patterns of GHR and the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway (JAK2, STAT3, STAT5A, and STAT5B) in human subcutaneous adipose tissue in relation to energy restriction and overfeeding.Tissue distribution was analyzed in a data set generated by RNA sequencing containing information on global expression in human tissues. Subcutaneous adipose tissue or adipocyte gene expression (measured by DNA microarrays) was investigated in the following settings: (i) individuals with obesity vs individuals with normal weight; (ii) energy restriction; and (iii) overfeeding.GHR expression was decreased in subjects with obesity compared with subjects with normal weight (P < 0.001). It was increased in response to energy restriction and decreased in response to overfeeding (P = 0.015 and P = 0.030, respectively). STAT3 expression was increased in subjects with obesity (P < 0.001). It was decreased during energy restriction and increased during overfeeding (P = 0.004 and P = 0.006, respectively). STAT3-regulated genes showed an overall view of overexpression in obesity.The results of the present study have shown that GHR, STAT3, and STAT3-regulated genes are dynamically, and reciprocally, regulated at the tissue level in response to energy restriction and overfeeding, suggesting that GH signaling is perturbed in obesity.

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