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Bioactive oxylipins in type 2 diabetes mellitus patients with and without hypertriglyceridemia

OBJECTIVE: Dyslipidemia, in particular elevated triglycerides (TGs) contribute to increased cardiovascular risk in type 2 diabetes mellitus (T2DM). In this pilot study we aimed to assess how increased TGs affect hepatic fat as well as polyunsaturated fatty acid (PUFA) metabolism and oxylipin formati...

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Autores principales: Xiao, Yanan, Pietzner, Anne, Rohwer, Nadine, Jung, Adelheid, Rothe, Michael, Weylandt, Karsten H., Elbelt, Ulf
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10472135/
https://www.ncbi.nlm.nih.gov/pubmed/37664847
http://dx.doi.org/10.3389/fendo.2023.1195247
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author Xiao, Yanan
Pietzner, Anne
Rohwer, Nadine
Jung, Adelheid
Rothe, Michael
Weylandt, Karsten H.
Elbelt, Ulf
author_facet Xiao, Yanan
Pietzner, Anne
Rohwer, Nadine
Jung, Adelheid
Rothe, Michael
Weylandt, Karsten H.
Elbelt, Ulf
author_sort Xiao, Yanan
collection PubMed
description OBJECTIVE: Dyslipidemia, in particular elevated triglycerides (TGs) contribute to increased cardiovascular risk in type 2 diabetes mellitus (T2DM). In this pilot study we aimed to assess how increased TGs affect hepatic fat as well as polyunsaturated fatty acid (PUFA) metabolism and oxylipin formation in T2DM patients. METHODS: 40 patients with T2DM were characterized analyzing routine lipid blood parameters, as well as medical history and clinical characteristics. Patients were divided into a hypertriglyceridemia (HTG) group (TG ≥ 1.7mmol/l) and a normal TG group with TGs within the reference range (TG < 1.7mmol/l). Profiles of PUFAs and their oxylipins in plasma were measured by gas chromatography and liquid chromatography/tandem mass spectrometry. Transient elastography (TE) was used to assess hepatic fat content measured as controlled attenuation parameter (CAP) (in dB/m) and the degree of liver fibrosis measured as stiffness (in kPa). RESULTS: Mean value of hepatic fat content measured as CAP as well as body mass index (BMI) were significantly higher in patients with high TGs as compared to those with normal TGs, and correlation analysis showed higher concentrations of TGs with increasing CAP and BMI scores in patients with T2DM. There were profound differences in plasma oxylipin levels between these two groups. Cytochrome P450 (CYP) and lipoxygenase (LOX) metabolites were generally more abundant in the HTG group, especially those derived from arachidonic acid (AA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), γ-linolenic acid (γ-LA), and α-linolenic acid (α-LA), and a strong correlation between TG levels and plasma metabolites from different pathways was observed. CONCLUSIONS: In adult patients with T2DM, elevated TGs were associated with increased liver fat and BMI. Furthermore, these patients also had significantly higher plasma levels of CYP- and LOX- oxylipins, which could be a novel indicator of increased inflammatory pathway activity, as well as a novel target to dampen this activity.
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spelling pubmed-104721352023-09-02 Bioactive oxylipins in type 2 diabetes mellitus patients with and without hypertriglyceridemia Xiao, Yanan Pietzner, Anne Rohwer, Nadine Jung, Adelheid Rothe, Michael Weylandt, Karsten H. Elbelt, Ulf Front Endocrinol (Lausanne) Endocrinology OBJECTIVE: Dyslipidemia, in particular elevated triglycerides (TGs) contribute to increased cardiovascular risk in type 2 diabetes mellitus (T2DM). In this pilot study we aimed to assess how increased TGs affect hepatic fat as well as polyunsaturated fatty acid (PUFA) metabolism and oxylipin formation in T2DM patients. METHODS: 40 patients with T2DM were characterized analyzing routine lipid blood parameters, as well as medical history and clinical characteristics. Patients were divided into a hypertriglyceridemia (HTG) group (TG ≥ 1.7mmol/l) and a normal TG group with TGs within the reference range (TG < 1.7mmol/l). Profiles of PUFAs and their oxylipins in plasma were measured by gas chromatography and liquid chromatography/tandem mass spectrometry. Transient elastography (TE) was used to assess hepatic fat content measured as controlled attenuation parameter (CAP) (in dB/m) and the degree of liver fibrosis measured as stiffness (in kPa). RESULTS: Mean value of hepatic fat content measured as CAP as well as body mass index (BMI) were significantly higher in patients with high TGs as compared to those with normal TGs, and correlation analysis showed higher concentrations of TGs with increasing CAP and BMI scores in patients with T2DM. There were profound differences in plasma oxylipin levels between these two groups. Cytochrome P450 (CYP) and lipoxygenase (LOX) metabolites were generally more abundant in the HTG group, especially those derived from arachidonic acid (AA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), γ-linolenic acid (γ-LA), and α-linolenic acid (α-LA), and a strong correlation between TG levels and plasma metabolites from different pathways was observed. CONCLUSIONS: In adult patients with T2DM, elevated TGs were associated with increased liver fat and BMI. Furthermore, these patients also had significantly higher plasma levels of CYP- and LOX- oxylipins, which could be a novel indicator of increased inflammatory pathway activity, as well as a novel target to dampen this activity. Frontiers Media S.A. 2023-08-17 /pmc/articles/PMC10472135/ /pubmed/37664847 http://dx.doi.org/10.3389/fendo.2023.1195247 Text en Copyright © 2023 Xiao, Pietzner, Rohwer, Jung, Rothe, Weylandt and Elbelt https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Endocrinology
Xiao, Yanan
Pietzner, Anne
Rohwer, Nadine
Jung, Adelheid
Rothe, Michael
Weylandt, Karsten H.
Elbelt, Ulf
Bioactive oxylipins in type 2 diabetes mellitus patients with and without hypertriglyceridemia
title Bioactive oxylipins in type 2 diabetes mellitus patients with and without hypertriglyceridemia
title_full Bioactive oxylipins in type 2 diabetes mellitus patients with and without hypertriglyceridemia
title_fullStr Bioactive oxylipins in type 2 diabetes mellitus patients with and without hypertriglyceridemia
title_full_unstemmed Bioactive oxylipins in type 2 diabetes mellitus patients with and without hypertriglyceridemia
title_short Bioactive oxylipins in type 2 diabetes mellitus patients with and without hypertriglyceridemia
title_sort bioactive oxylipins in type 2 diabetes mellitus patients with and without hypertriglyceridemia
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10472135/
https://www.ncbi.nlm.nih.gov/pubmed/37664847
http://dx.doi.org/10.3389/fendo.2023.1195247
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