ECE2022 Poster Presentations Pituitary and Neuroendocrinology (127 abstracts)
Gene expression profiling of subcutaneous adipose tissue reveals new biomarkers in active acromegaly
Camilla Maria Falch 1,2,3 , Mai C. Arlien-Søborg 4,5 , Jakob Dal 4,5 , Arvind Sundaram 6 , Annika E. Michelsen 3 , Thor Ueland 3 , Linn G. Olsen 1,3 , Ansgar Heck 1,2 , Jens Bollerslev 1,2 , Jens Otto Jorgensen 4,5 & Cristina Olarescu 1,2,3
1Oslo University Hospital, Section of Specialized Endocrinology, Department of Endocrinology, Oslo, Norway; 2University of Oslo, Institute for Clinical Medicine, Faculty of Medicine, Oslo, Norway; 3Oslo University Hospital, Research Institute for Internal Medicine, Oslo, Norway; 4Aarhus University Hospital, Department of Endocrinology and Internal Medicine, Aarhus, Denmark; 5Aarhus University Hospital, Medical Research Laboratory, Department of Clinical Medicine, Aarhus, Denmark; 6Oslo University Hospital, Department of Medical Genetics, University of Oslo., Oslo, Norway
Objective: Patients with acromegaly present increased insulin resistance despite reduced adipose tissue (AT) mass. Growth hormone (GH) stimulates lipolysis, but the role of AT as a metabolic factor in patients with acromegaly is still uncertain. Moreover, there is a need for better biomarkers of disease activity in acromegaly.
Methods: RNA-sequencing was performed on paired subcutaneous AT (SAT) biopsies from patients (n=6) with active acromegaly and after disease control obtained by surgery. Clustering and pathway analyses were investigated. HTRA1, METRNL, S100A8, S100A9, PDGFD, PTX3, MMP9, TEK, ANGPT1, GRN and FLT1 and corresponding proteins were selected for further analyses. In a lager patient cohort (n=23), serum proteins were measured by immunoassay. Correlations between GH, insulin like growth factor-I (IGF-I), and visceral AT (VAT), SAT, total AT and serum proteins were analyzed. The in vitro effects of GH and IGF-I stimulation on the gene expression of HTRA1, METRNL, S100A8, S100A9 and PDGFD in human subcutaneous adipocytes, endothelial cells (HUVEC) and monocytes (THP-1) were investigated.
Results: 743 genes were significantly differentially expressed (470 genes downregulated, 273 upregulated after disease control, p-adjusted <0.05). The patients clustered according to disease activity. Pathways related to growth hormone activity, extracellular matrix deposition/adhesion/collagen, and inflammation/vascularization were among the differentially expressed signaling pathways. Of notice, several collagen genes were upregulated in active disease. Serum levels of HTRA1, METRNL, S100A8, S100A9, and PDGFD significantly decreased after disease control (P<0.05). HTRA1, S100A8 and S100A9 correlated with VAT (0.725<R<0.551, P<0.05). In vitro GH and IGF-I stimulation of subcutaneous adipocytes and HUVEC did not change gene expression of HTRA1, METRNL, S100A8, S100A9 and PDGFD. METRNL was increased by IGF-I in THP-1 monocytes.
Conclusion: Disease activity has a stronger impact on the mRNA signature of SAT that overplays the inter-individual differences. Novel candidate genes upregulated in SAT of active acromegaly were identified. Among them, HTRA1, METRNL, S100A8, S100A9 and PDGFD can represent potential biomarkers for disease activity and metabolic risk factors in acromegaly.
Article tools
My recent searches
My recently viewed abstracts
Authors
Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
© Bioscientifica 2024 |
Privacy policy |
Cookie settings
BiosciAbstracts
Bioscientifica Abstracts is the gateway to a series of products that provide a permanent, citable record of abstracts for biomedical and life science conferences.
Find out more