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Expression of GHR and Downstream Signaling Genes in Human Adipose Tissue-Relation to Obesity and Weight Change
Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
Univ Gothenburg, Sweden.
Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Cityhälsan Centrum, Norrköping.ORCID iD: 0000-0002-1680-1000
Univ Gothenburg, Sweden.
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2019 (English)In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 104, no 5, p. 1459-1470Article in journal (Refereed) Published
Abstract [en]

Context: 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. Objective: 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. Design, Patients, and Interventions: 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. Results: GHR expression was decreased in subjects with obesity compared with subjects with normal weight (P amp;lt; 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 amp;lt; 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. Conclusions: 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.

Place, publisher, year, edition, pages
ENDOCRINE SOC , 2019. Vol. 104, no 5, p. 1459-1470
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Genetics
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URN: urn:nbn:se:liu:diva-158997DOI: 10.1210/jc.2018-01036ISI: 000473692100014PubMedID: 30541116OAI: oai:DiVA.org:liu-158997DiVA, id: diva2:1338114
Note

Funding Agencies|Swedish Research Council [2017-01707]; Sahlgrenska University Hospital Regional Agreement on Medical Education and Research

Available from: 2019-07-19 Created: 2019-07-19 Last updated: 2019-07-19

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Nyström, Fredrik H
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Division of Cardiovascular MedicineFaculty of Medicine and Health SciencesPrimary Health Care Center Cityhälsan Centrum, Norrköping
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