Abstract
Although severe obesity is associated with insulin resistance (IR) and inflammation, secretory function of intra-abdominal adipose tissues and their relationships with IR and inflammation markers remain poorly understood. Aims were to measure gene expression of adipogenic (C/EBPα/β, PPARγ-1/2, SREBP-1c, LXRα), lipogenic (SCD1, DGAT-1/2), angiogenic (VEGFα, leptin), and fibrotic (LOX, COL6A3) factors in the round ligament (RL), omental (OM), and mesenteric (ME) fat depots and to evaluate their relationships with IR and inflammation markers in 48 women with severe obesity undergoing bariatric surgery. Gene expression was assessed by RT-qPCR, and plasma glucose and insulin (HOMA-IR calculated), PAI-1, IL-6, TNFα, adiponectin, and leptin levels were determined. C/EBPβ and PPARγ-1/2 mRNA levels were more expressed in the OM (0.001<p<0.05). ME showed the highest expression of C/EBPα, SREBP-1c, DGAT-2, and leptin and the lowest of SCD1, LXRα, VEGFα, and LOX (0.001<p<0.05). COL6A3 expression was higher in the ME and RL (p<0.001). COL6A3 expression was negatively associated with IR indices in the RL (0.01<p<0.05) and with fasting glycemia and HOMA-IR in the OM (0.001<p<0.05). VEGFα expression was positively related to TNFα and PAI-1 in the RL (0.001<p<0.05) and to PAI-1 in the OM (p<0.05) and negatively to PAI-1 in the ME (p<0.001). Fibrosis gene expression correlated negatively with inflammation in RL and OM (0.001<p<0.05) and positively with PAI-1 in the ME (0.001<p<0.05). The varying relationships of gene expression profiles with selected IR indices and inflammation biomarkers further suggest these fat depots have distinct contributions to overall health in premenopausal women with severe obesity.
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Acknowledgements
The severely obese cohort was supported, over the years, by the Laval University Merck-Frosst/CIHR Research Chair in Obesity. The exceptional contribution year after year of Dr Simon Biron in the bariatric surgeries as well as in the collection of the different tissue samples of all patients involved in this project is largely recognized and gratefully acknowledged through this manuscript. The cooperation of subjects who participated to this study is also greatly appreciated. Special thanks are also expressed to Dr. Fanny Therrien and her colleagues for their very helpful assistance in AT and plasma bank management.
Funding
This work was supported by the operating grant OHP # 67388 obtained from the Canadian Institutes of Health Research by Pascale Mauriège as well by the grant #20882 (Catherine Mounier, Denis R. Joanisse, and Pascale Mauriège) received from the Foundation of the Centre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec (CRIUCPQ). Andrée-Anne Clément was a master scholarship recipient from the CRIUCPQ and obtained a distinction from the 15th French-Spanish Meeting of the Consortium Trans-Pyrénéen Obésité-Diabète (CTPIOD), Toulouse, France, July 2018, for her oral presentation of some of these data.
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AAC was involved in laboratory experiments, analysis, and interpretation of the data, as well as in writing of the manuscript. ML supervised laboratory experiments, and MAL helped ML in the design of probes involved in AT gene lipogenesis. IL and JB provided the equipment and resources for the plasma assays of adipokines and PAI-1. LDB as the co-head of the bariatric surgery chair of the CRIUCPQ and DR, director of the CRIUCPQ, allowed the constitution of the AT bank from which we were able to carry out this study. CM and DRJ were co-applicants of the funds obtained from the CRIUCPQ. DRJ, co-supervisor of AAC, was more particularly in charge of statistical analyses and their interpretation. PM, supervisor of AAC, obtained the CIHR initial funding and the one from the CRIUCPQ. She was also in charge of the experimental design of the study, from analyzing and interpreting data to writing the manuscript.
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The experimental design of this study was approved by our local hospital and university ethics committees, i.e., the Laval University Research Ethics Committee (CERUL: Comité d’Ethique de la Recherche de l’Université Laval) #2004-108.
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Key points
1) Three intra-abdominal adipose depots display different secretory function.
2) The OM fat shows higher adipogenesis expression, suggesting its ongoing expansion.
3) Secretory function of adipose tissues correlates with IR and inflammation markers.
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Clément, AA., Lacaille, M., Lounis, M.A. et al. Intra-abdominal adipose depot variation in adipogenesis, lipogenesis, angiogenesis, and fibrosis gene expression and relationships with insulin resistance and inflammation in premenopausal women with severe obesity. J Physiol Biochem 78, 527–542 (2022). https://doi.org/10.1007/s13105-021-00855-4
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DOI: https://doi.org/10.1007/s13105-021-00855-4