The impact of metabolic endotoxaemia on the browning process in human adipocytes

Farah Omran, Alice M. Murphy, Awais Z. Younis, Ioannis Kyrou, Jana Vrbikova, Vojtech Hainer, Petra Sramkova, Martin Fried, Graham Ball, Gyanendra Tripathi, Sudhesh Kumar, Philip G. McTernan, Mark Christian

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)
22 Downloads (Pure)

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.
Original languageEnglish
Article number154
Number of pages17
JournalBMC Medicine
Volume21
Issue number1
Early online date19 Apr 2023
DOIs
Publication statusE-pub ahead of print - 19 Apr 2023

Bibliographical note

This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory
regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.

Keywords

  • Obesity
  • Endotoxin
  • Adipocyte browning
  • Mitochondria
  • Lipopolysaccharide
  • Human adipocytes
  • Bariatric surgery

Fingerprint

Dive into the research topics of 'The impact of metabolic endotoxaemia on the browning process in human adipocytes'. Together they form a unique fingerprint.

Cite this