BES2021 Belgian Endocrine Society 2021 Abstracts (26 abstracts)
Identification of myokines potentially involved in the improvement of glucose homeostasis induced by bariatric surgery
Orioli Laura 1,2 , Derop Julien 3 , Canouil Mickaël 3 , Sawadogo Kiswendsida 4 , Deldicque Louise 5 , Lause Pascale 1 , de Barsy Marie 2 , Loumaye Audrey 1,2 , Deswysen Yannick 6 , Navez Benoit 6 , Bonnefond Amélie 3 & Thissen Jean-Paul 1,2
1Institute of Experimental and Clinical Research (IREC), Endocrinology, Diabetes and Nutrition (EDIN), Université Catholique de Louvain (UCLouvain), Brussels, Belgium; 2Department of Endocrinology and Nutrition, Cliniques Universitaires Saint-Luc, Brussels, Belgium; 3Inserm U1283, CNRS UMR 8199, European Genomic Institute for Diabetes, Institut Pasteur de Lille, Lille France; 4Statistical Support Unit, King Albert II Cancer and Hematology Institute, Cliniques Universitaires Saint-Luc, Brussels, Belgium; 5Institute of NeuroScience (IONS), Université Catholique de Louvain (UCLouvain), 1348 Louvain-La-Neuve, Belgium; 6Department of Oeso-gastro-duodenal and bariatric surgery, Cliniques Universitaires Saint-Luc, Brussels, Belgium
Background and aims: The contribution of myokines to improved glucose homeostasis induced by bariatric surgery is unknown. Our study aims to identify myokines potentially improving glucose homeostasis following bariatric surgery.
Patients and methods: Obese insulin-resistant patients were evaluated before and 3 months after bariatric surgery, i.e. a sleeve gastrectomy or a Roux-en-Y gastric bypass (n62). Muscle biopsies were taken from vastus lateralis (n = 39). Glucose homeostasis was evaluated using the HOMA test. Changes in muscle transcriptome were determined by RNA-Seq (n12). Genes encoding myokines were identified based on the prediction of a signal peptide and annotations. Changes in myokines expression identified by RNA-seq were replicated by RT-qPCR (n39).
Results: Thirty-six (58%) of the 62 patients included in the study were females and 39 (63%) underwent a sleeve gastrectomy. The mean age (±SD) was 44 (±11) years and the median pre-operative BMI [IQR] was 42.6 [40.7-44.4] kg/m2. All the clinical and biological parameters were significantly improved after surgery except for HDL cholesterol. In particular, insulin sensitivity was significantly increased after surgery (HOMA-S +34.2%, P < 0.0001). The RNA-Seq study identified 1363 single genes whose expression was changed by surgery (FDR≤0.10). Among those, 41 up-regulated (FC≥1.3) and 56 down-regulated (FC≤0.7) genes encoded myokines. Increased expression of CX3CL1 (+73%, P < 0.0001), ADAMTS9 (+35%, P < 0.0001), BDNF (+30%, p 0.006) and ANG (+29%, P < 0.0001) as well as decreased expression of MSTN (-45%, P < 0.0001) and FNDC5 (-25%, P < 0.0001), genes encoding myokines known to regulate glucose homeostasis, were confirmed by RT-qPCR. Increased expression of NTE5 (+28%, p 0.001), BMP8B (+67%, P < 0.0001), TNFRSF10B (+34%, P < 0.0001), SDC4 (+25, p 0.003), and KDR (+39%, P < 0.0001) as well as decreased expression of DLK1 (-32%, P < 0.0001), genes encoding myokines related to obesity and/or type 2 diabetes, were also confirmed. RT-qPCR analysis also showed a significantly reduced expression of MYH1 (-38%, p 0.002) and a significant increased expression of MYH2 (+21%, p 0.022).
Conclusions: Our study shows that bariatric surgery changes the muscle transcriptome and the expression of myokines, either known to regulate glucose homeostasis (fractalkine, ADAMTS9, BNDF, angiogenin, myostatin, irisin) or related to obesity/type 2 diabetes (NTE5, BMP8B, TNFRSF10B, SDC4, KDR, DLK1). The changes in the expression of myosin heavy chains suggest a less fast muscle phenotype after surgery. We are currently working at 1) measuring plasma levels of myostatin (MSTN) and fractalkine (CX3CL1), 2) identifying myokines potentially regulating glucose homeostasis using multivariate linear regression analysis, and 3) analyzing enriched pathways using Gene Set Enrichment Analysis.
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Endocrine Abstracts
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