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

Yanan Xiao; Anne Pietzner; Nadine Rohwer; Adelheid Jung; Michael Rothe; Karsten H Weylandt; Ulf Elbelt

doi:10.3389/fendo.2023.1195247

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

Front Endocrinol (Lausanne). 2023 Aug 17:14:1195247. doi: 10.3389/fendo.2023.1195247. eCollection 2023.

Authors

Yanan Xiao^{1

2}, Anne Pietzner^{1

3}, Nadine Rohwer^{1

3

4}, Adelheid Jung¹, Michael Rothe⁵, Karsten H Weylandt^{1

3}, Ulf Elbelt^{1

2}

Affiliations

¹ Division of Medicine, Department of Gastroenterology, Metabolism and Oncology, University Hospital Ruppin-Brandenburg, Brandenburg Medical School, Neuruppin, Germany.
² Medical Department, Division of Psychosomatic Medicine, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
³ Faculty of Health Sciences, Joint Faculty of the Brandenburg University of Technology, Brandenburg Medical School and University of Potsdam, Potsdam, Germany.
⁴ Department of Molecular Toxicology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.
⁵ Lipidomix, Berlin, Germany.

Abstract

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.

Keywords: controlled attenuation parameter; hypertriglyceridemia; oxylipins; polyunsaturated fatty acids; type 2 diabetes mellitus.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Diabetes Mellitus, Type 2* / complications
Humans
Hypertriglyceridemia* / complications
Liver
Oxylipins
Pilot Projects

Substances

Oxylipins

Grants and funding

This project was supported by funds from the Ministry of Science, Research and Culture of the State of Brandenburg and by the Brandenburg Medical School (Medizinische Hochschule Brandenburg, MHB) publication fund supported by the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG), and Open Access Publication Fund of Charité - Universitätsmedizin Berlin.