Evaluation of various biomarkers as potential mediators of the association between Δ5 desaturase, Δ6 desaturase, and stearoyl-CoA desaturase activity and incident type 2 diabetes in the European Prospective Investigation into Cancer and Nutrition–Potsdam Study

Jacobs, Simone; Schiller, Katja; Jansen, Eugène; Boeing, Heiner; Schulze, Matthias B.; Kröger, Janine

doi:10.3945/ajcn.114.102707

Cited by 48 publications

(50 citation statements)

References 51 publications

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“…As DGLA is synthesized from linoleic acid by ⊿6-desaturase and chain elongation enzyme, and then is converted to ARA by ⊿5-desaturase, these changes in plasma lipid fatty acid composition are consistent with increased ⊿6-desaturase and decreased ⊿5-desaturase activities [81] . These DM-associated changes in the proportion of eicosanoid precursors in plasma lipids may represent a part of our body's adaptive mechanism, because PGE 1 from DGLA is vasodilative and PGE 2 from ARA is vasoconstrictive.…”

Section: Correlation Of Plasma Lipid Fatty Acid Composition With Dmmentioning

confidence: 81%

Medicines and Vegetable Oils as Hidden Causes of Cardiovascular Disease and Diabetes

Okuyama

Langsjoen²,

Ohara

et al. 2016

Pharmacology

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Background: Positive associations have been observed between cardiovascular disease (CVD) and type 2 diabetes mellitus (DM), but their causal relationship has not been clarified. Nevertheless, guidelines from relevant medical societies recommend using cholesterol lowering medication (statin) for both types of patients. Medicines with several different action mechanisms have been developed, and the effectiveness of different lifestyle modifications has been studied extensively for the prevention of DM, which was successful in improving clinical marker status in relatively short-term treatments, but none have been shown to be effective in improving long-term outcomes (mortality from CVD and all causes). Summary: Statin-induced suppression of prenyl intermediates in the cholesterol biosynthetic pathway has been linked to stimulated atherosclerosis and heart failure. On the other hand, certain types of vegetable oil and hydrogenated oil shortened the survival of stroke-prone spontaneously hypertensive rats by decreasing platelet number, increasing hemorrhagic tendency and damaging kidney functions, which could not be accounted for by their fatty acid and phytosterol compositions. These vegetable oils and medicines such as statin and warfarin share, in part, a common mechanism to inhibit vitamin K₂-dependent processes, which was interpreted to lead to increased onset of CVD, DM, chronic kidney disease, bone fracture and even mental disorder. Impaired vitamin K₂-dependent processes by some types of vegetable oils and medicines, but not plasma high low density lipoprotein cholesterol, were proposed as the cause of CVD, DM and other lifestyle-related diseases. High n-6/n-3 fatty acid ratio of ingested foods, but not animal fats, was emphasized to be another risk factor for many of the diseases described above. Key Messages: To date, no randomized controlled trials (RCTs) have been performed to prove the above interpretation. However, the opposite types of RCT trials have been performed by increasing the intake of high-linoleic vegetable oils and reducing that of animal fats, which resulted in increased CVD and all-cause mortality. The amounts of these vegetable oils to exhibit adverse effects in animal studies are not huge (<6 energy %), which should not be overlooked nor disregarded.

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Section: Correlation Of Plasma Lipid Fatty Acid Composition With Dmmentioning

confidence: 81%

Medicines and Vegetable Oils as Hidden Causes of Cardiovascular Disease and Diabetes

Okuyama

Langsjoen²,

Ohara

et al. 2016

Pharmacology

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“…It is known that both LA and ALA belonging to different families of PUFAs compete for the same set of enzymes of desaturases and elongases [18–20]. Changes in the activities of Δ 6 and Δ 5 desaturases in DM has been correlated to the lower content of AA and higher content of LA in almost all the tissues except brain [21, 22]. In experimental animals induced to develop type 2 DM and patients with type 2 DM, the changes in the activities of Δ 6 and Δ 5 desaturases have been variable [22–25], but data indicate that type 2 DM (at least in patients with long standing disease and poor glycemic control) negatively affects Δ 5 desaturases activity and ω6/ω3 PUFAs balance [18, 26].…”

Section: Resultsmentioning

confidence: 99%

Long chain polyunsaturated fatty acids (LCPUFAs) and nordihydroguaiaretic acid (NDGA) modulate metabolic and inflammatory markers in a spontaneous type 2 diabetes mellitus model (Stillman Salgado rats)

et al. 2016

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BackgroundDiabetes mellitus (DM) is a complex disease with alterations in metabolic and inflammatory markers. Stillman Salgado rats (eSS) spontaneously develop type 2 DM by middle age showing progressive impairment of glucose tolerance with hyperglycemia, hypertriglyceridemia and hyperinsulinemia. We analyzed the effects of supplementation of ω-3 and ω-6 polyunsaturated fatty acids (PUFAs) with or without nordihydroguaiaretic acid (NDGA) added, an antioxidant and lipoxygenase inhibitor, on metabolic and inflammatory parameters in eSS rats to evaluate whether they can delay development and/or prevent progression of DM.MethodsAfter weaning, eSS rats received, intraperitoneally, once a month ω-3 (EPA 35% and DHA 40%–6.25 mg/Kg) or ω-6 (90% arachidonic acid- 6. 25 mg/Kg) for twelve months. Two additional groups of rats received 1.9 mg/kg NDGA added to ω-3 and ω-6 fatty acids. Blood samples were collected at day 40, and at the end of the 6th month and 12th month of age to determine plasma triglycerides (TGs), total plasma fatty acids (FA), A1C hemoglobin (HbA1C), C-reactive protein (CRP), gamma glutamyl transpeptidase (GGT), lipo and hydro peroxides, nitrites and IL-6 (in plasma and liver, kidney, and pancreas) and underwent oral glucose tolerance test (OGTT) as well. Wistar and eSS rats that received saline solution were used as controls.ResultsPlasma lipids profile, TG, fasting and post-prandial blood glucose levels, and glycosylated HbA1C showed significant improvements in ω-3 and ω-3 + NDGA treated animals compared to eSS control group. ω-3 and ω-3 + NDGA groups showed an inverse correlation with fasting blood glucose and showed lower plasma levels of GGT, TG, and CRP. eSS rats treated with ω-3 LCPUFAs showed reduced level of inflammatory and oxidative indices in plasma and liver, kidney and pancreas tissues in comparison with eSS control (non-treated) and ω-6 treated groups.ConclusionseSS rats are a useful model to study type 2 DM pathophysiology and related inflammatory indices. ω-3 + NDGA supplementation, at the doses tested, ameliorated inflammatory, metabolic and oxidative stress markers studied.

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“…In line with our previous EMFA findings [25], our results suggest that fatty acids (except for SFAs) may affect the risk of type 2 diabetes in a manner largely independent of insulin sensitivity and insulin secretion. Accumulation of liver fat and dyslipidemia could be other possible mechanisms to explain the associations of estimated SCD, D6D and D5D activities with type 2 diabetes risk [50].…”

Section: Discussionmentioning

confidence: 99%

Plasma fatty acids as predictors of glycaemia and type 2 diabetes

et al. 2015

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Aims/hypothesis Our aim was to investigate the fasting proportions of fatty acids and estimated desaturase and elongase activities in three different lipid fractions in plasma, phospholipids (PLs), cholesteryl esters (CEs) and triacylglycerols (TGs), as predictors for the worsening of glycaemia (area under the glucose curve in an OGTT [glucose AUC]) and incident type 2 diabetes in a 5.9 year follow-up of the Metabolic Syndrome in Men population-based cohort. Methods Fatty acid proportions were measured in plasma PL, CE and TG fractions in 1,364 Finnish men aged 45-68 years at baseline. The prospective follow-up study included only men who were non-diabetic at baseline and had data available at follow-up (n=1,302). A total of 71 participants developed new type 2 diabetes during follow-up.Results After adjusting for confounding factors, total saturated fatty acids, palmitoleic acid (16:1n-7), dihomo-γ-linolenic acid (20:3n-6) and estimated stearoyl-CoA desaturase 1 and Δ 6 -desaturase (D6D) enzyme activities significantly predicted the worsening of glycaemia whereas total polyunsaturated fatty acid, linoleic acid (18:2n-6) and elongase activity predicted a decrease in the glucose AUC. Estimated D6D activity and dihomo-γ-linolenic acid (20:3n-6) were associated with an increased risk of incident type 2 diabetes. Results were consistent across the three different lipid fractions. However, fatty acid proportions in the PL and CE fractions were stronger predictors for glycaemia and incident type 2 diabetes compared with fatty acid proportions in the TG fraction. Conclusions/interpretation Selected fatty acid proportions of plasma lipid fractions and their ratios, which reflect desaturase and elongase enzyme activities, may be good biomarkers for the worsening of glycaemia and incident type 2 diabetes.

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Evaluation of various biomarkers as potential mediators of the association between Δ5 desaturase, Δ6 desaturase, and stearoyl-CoA desaturase activity and incident type 2 diabetes in the European Prospective Investigation into Cancer and Nutrition–Potsdam Study

Abstract: Liver fat accumulation, as reflected by the FLI, and dyslipidemia, as reflected by triglycerides, may partly explain the association between estimated D5D, D6D, and SCD activity and T2D risk.

Cited by 48 publications

References 51 publications

Medicines and Vegetable Oils as Hidden Causes of Cardiovascular Disease and Diabetes

Medicines and Vegetable Oils as Hidden Causes of Cardiovascular Disease and Diabetes

Long chain polyunsaturated fatty acids (LCPUFAs) and nordihydroguaiaretic acid (NDGA) modulate metabolic and inflammatory markers in a spontaneous type 2 diabetes mellitus model (Stillman Salgado rats)

Plasma fatty acids as predictors of glycaemia and type 2 diabetes

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