Metabolic adaptations in severe obesity: Insights from circulating oxylipins before and after weight loss.
Bariatric surgery
Cyclooxygenase
Lipoxygenase
Metaflammation
Polyunsaturated fatty acids
Weight loss
Journal
Clinical nutrition (Edinburgh, Scotland)
ISSN: 1532-1983
Titre abrégé: Clin Nutr
Pays: England
ID NLM: 8309603
Informations de publication
Date de publication:
06 Dec 2023
06 Dec 2023
Historique:
received:
26
06
2023
revised:
29
11
2023
accepted:
04
12
2023
medline:
16
12
2023
pubmed:
16
12
2023
entrez:
15
12
2023
Statut:
aheadofprint
Résumé
The relationship between lipid mediators and severe obesity remains unclear. Our study investigates the impact of severe obesity on plasma concentrations of oxylipins and fatty acids and explores the consequences of weight loss. In the clinical trial identifier NCT05554224 study, 116 patients with severe obesity and 63 overweight/obese healthy controls matched for age and sex (≈2:1) provided plasma. To assess the effect of surgically induced weight loss, we requested paired plasma samples from 44 patients undergoing laparoscopic sleeve gastrectomy one year after the procedure. Oxylipins were measured using ultra-high-pressure liquid chromatography coupled to a triple quadrupole mass spectrometer via semi-targeted lipidomics. Cytokines and markers of interorgan crosstalk were measured using enzyme-linked immunosorbent assays. We observed significantly elevated levels of circulating fatty acids and oxylipins in patients with severe obesity compared to their metabolically healthier overweight/obese counterparts. Our findings indicated that sex and liver disease were not confounding factors, but we observed weak correlations in plasma with circulating adipokines, suggesting the influence of adipose tissue. Importantly, while weight loss restored the balance in circulating fatty acids, it did not fully normalize the oxylipin profile. Before surgery, oxylipins derived from lipoxygenase activity, such as 12-HETE, 11-HDoHE, 14-HDoHE, and 12-HEPE, were predominant. However, one year following laparoscopic sleeve gastrectomy, we observed a complex shift in the oxylipin profile, favoring species from the cyclooxygenase pathway, particularly proinflammatory prostanoids like TXB2, PGE2, PGD2, and 12-HHTrE. This transformation appears to be linked to a reduction in adiposity, underscoring the role of lipid turnover in the development of metabolic disorders associated with severe obesity. Despite the reduction in fatty acid levels associated with weight loss, the oxylipin profile shifts towards a predominance of more proinflammatory species. These observations underscore the significance of seeking mechanistic approaches to address severe obesity and emphasize the importance of closely monitoring the metabolic adaptations after weight loss.
Sections du résumé
BACKGROUND
BACKGROUND
The relationship between lipid mediators and severe obesity remains unclear. Our study investigates the impact of severe obesity on plasma concentrations of oxylipins and fatty acids and explores the consequences of weight loss.
METHODS
METHODS
In the clinical trial identifier NCT05554224 study, 116 patients with severe obesity and 63 overweight/obese healthy controls matched for age and sex (≈2:1) provided plasma. To assess the effect of surgically induced weight loss, we requested paired plasma samples from 44 patients undergoing laparoscopic sleeve gastrectomy one year after the procedure. Oxylipins were measured using ultra-high-pressure liquid chromatography coupled to a triple quadrupole mass spectrometer via semi-targeted lipidomics. Cytokines and markers of interorgan crosstalk were measured using enzyme-linked immunosorbent assays.
RESULTS
RESULTS
We observed significantly elevated levels of circulating fatty acids and oxylipins in patients with severe obesity compared to their metabolically healthier overweight/obese counterparts. Our findings indicated that sex and liver disease were not confounding factors, but we observed weak correlations in plasma with circulating adipokines, suggesting the influence of adipose tissue. Importantly, while weight loss restored the balance in circulating fatty acids, it did not fully normalize the oxylipin profile. Before surgery, oxylipins derived from lipoxygenase activity, such as 12-HETE, 11-HDoHE, 14-HDoHE, and 12-HEPE, were predominant. However, one year following laparoscopic sleeve gastrectomy, we observed a complex shift in the oxylipin profile, favoring species from the cyclooxygenase pathway, particularly proinflammatory prostanoids like TXB2, PGE2, PGD2, and 12-HHTrE. This transformation appears to be linked to a reduction in adiposity, underscoring the role of lipid turnover in the development of metabolic disorders associated with severe obesity.
CONCLUSIONS
CONCLUSIONS
Despite the reduction in fatty acid levels associated with weight loss, the oxylipin profile shifts towards a predominance of more proinflammatory species. These observations underscore the significance of seeking mechanistic approaches to address severe obesity and emphasize the importance of closely monitoring the metabolic adaptations after weight loss.
Identifiants
pubmed: 38101315
pii: S0261-5614(23)00424-7
doi: 10.1016/j.clnu.2023.12.002
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
246-258Informations de copyright
Copyright © 2023 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.
Déclaration de conflit d'intérêts
Conflict of interest The authors declare that there are no competing interests in disclosing personal or financial interests, and there are no external factors potentially affecting the objectivity and quality of the information.