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The impact of metabolic endotoxaemia on the browning process in human adipocytes
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Omran, Farah, Murphy, Alice M., Younis, Awais Z., Kyrou, Ioannis, Vrbikova, Jana, Hainer, Vojtech, Sramkova, Petra, Fried, Martin, Ball, Graham, Tripathi, Gyanendra, Kumar, Sudhesh, McTernan, Philip G. and Christian, Mark (2023) The impact of metabolic endotoxaemia on the browning process in human adipocytes. BMC Medicine, 21 (1). 154. doi:10.1186/s12916-023-02857-z ISSN 1741-7015.
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WRAP-impact-metabolic-endotoxaemia-browning-process-human-adipocytes-2023.pdf - Published Version - Requires a PDF viewer. Available under License Creative Commons Attribution 4.0. Download (1948Kb) | Preview |
Official URL: https://doi.org/10.1186/s12916-023-02857-z
Abstract
Background: Dysfunctional adipose tissue (AT) is known to contribute to the pathophysiology of metabolic disease, including type 2 diabetes mellitus (T2DM). This dysfunction may occur, in part, as a consequence of gut-derived endotoxaemia inducing changes in adipocyte mitochondrial function and reducing the proportion of BRITE (brown-in-white) adipocytes. Therefore, the present study investigated whether endotoxin (lipopolysaccharide; LPS) directly contributes to impaired human adipocyte mitochondrial function and browning in human adipocytes, and the relevant impact of obesity status pre and post bariatric surgery. Methods: Human differentiated abdominal subcutaneous (AbdSc) adipocytes from participants with obesity and normal-weight participants were treated with endotoxin to assess in vitro changes in mitochondrial function and BRITE phenotype. Ex vivo human AbdSc AT from different groups of participants (normal-weight, obesity, pre- and 6 months post-bariatric surgery) were assessed for similar analyses including circulating endotoxin levels. Results: Ex vivo AT analysis (lean & obese, weight loss post-bariatric surgery) identified that systemic endotoxin negatively correlated with BAT gene expression (p < 0.05). In vitro endotoxin treatment of AbdSc adipocytes (lean & obese) reduced mitochondrial dynamics (74.6% reduction; p < 0.0001), biogenesis (81.2% reduction; p < 0.0001) and the BRITE phenotype (93.8% reduction; p < 0.0001). Lean AbdSc adipocytes were more responsive to adrenergic signalling than obese AbdSc adipocytes; although endotoxin mitigated this response (92.6% reduction; p < 0.0001). Conclusions: Taken together, these data suggest that systemic gut-derived endotoxaemia contributes to both individual adipocyte dysfunction and reduced browning capacity of the adipocyte cell population, exacerbating metabolic consequences. As bariatric surgery reduces endotoxin levels and is associated with improving adipocyte functionality, this may provide further evidence regarding the metabolic benefits of such surgical interventions.
Item Type: | Journal Article | |||||||||||||||
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Subjects: | Q Science > QP Physiology R Medicine > RC Internal medicine R Medicine > RD Surgery |
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Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Dean's Office & Professional Support Services Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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SWORD Depositor: | Library Publications Router | |||||||||||||||
Library of Congress Subject Headings (LCSH): | Obesity, Endotoxins, Fat cells, Mitochondria, Obesity -- Surgery | |||||||||||||||
Journal or Publication Title: | BMC Medicine | |||||||||||||||
Publisher: | BioMed Central Ltd. | |||||||||||||||
ISSN: | 1741-7015 | |||||||||||||||
Official Date: | 19 April 2023 | |||||||||||||||
Dates: |
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Volume: | 21 | |||||||||||||||
Number: | 1 | |||||||||||||||
Article Number: | 154 | |||||||||||||||
DOI: | 10.1186/s12916-023-02857-z | |||||||||||||||
Status: | Peer Reviewed | |||||||||||||||
Publication Status: | Published | |||||||||||||||
Access rights to Published version: | Open Access (Creative Commons) | |||||||||||||||
Date of first compliant deposit: | 21 April 2023 | |||||||||||||||
Date of first compliant Open Access: | 21 April 2023 | |||||||||||||||
RIOXX Funder/Project Grant: |
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