Reduction of n-3 PUFAs, specifically DHA and EPA, and enhancement of peroxisomal beta-oxidation in type 2 diabetic rat heart

Hou, Lianguo; Lian, Kaoqi; Yao, Min; Shi, Yun; Lu, Xinxin; Fang, Lijia; He, Tianbo; Jiang, Lingling

doi:10.1186/1475-2840-11-126

Cited by 39 publications

(37 citation statements)

References 35 publications

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“…This is consistent with data from a rodent model of type 2 diabetes mellitus, in which myocardial content EPA and DHA was lower in rats with type 2 diabetes mellitus and may therefore be a factor associated with cardiac pathophysiology in type 2 diabetes mellitus [40]. …”

Section: Discussionsupporting

confidence: 91%

Effects of icosapent ethyl on lipid and inflammatory parameters in patients with diabetes mellitus-2, residual elevated triglycerides (200–500 mg/dL), and on statin therapy at LDL-C goal: the ANCHOR study

Brinton

Ballantyne

Bays

et al. 2013

Cardiovasc Diabetol

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BackgroundIcosapent ethyl (IPE) is a high-purity prescription form of eicosapentaenoic acid (EPA) ethyl ester indicated as an adjunct to diet to reduce triglyceride (TG) levels in adult patients with severe (≥500 mg/dL) hypertriglyceridemia. ANCHOR was a 12-week, phase 3 study that evaluated the efficacy and safety of IPE in patients (N = 702) with residual high fasting TG levels (≥200 and <500 mg/dL) despite having optimized low-density lipoprotein cholesterol (LDL-C) levels (≥40 and <100 mg/dL) on statin therapy. Among patients randomized to IPE (4 g/day or 2 g/day) or placebo, 514 (73%) had diabetes mellitus.MethodsA post hoc subgroup analysis of the ANCHOR study was conducted to assess the effects of IPE on median placebo-adjusted percent change from baseline in efficacy end point parameters in 3 subgroups: total (all subjects with diabetes—overall median baseline glycosylated hemoglobin A1c [A1c] = 6.8%), better-controlled diabetes (below median baseline A1c), and less-controlled diabetes (above median baseline A1c).ResultsBaseline efficacy parameters were similar among all groups except high-sensitivity C-reactive protein (hsCRP), which was higher in the total and less-controlled diabetes groups. Compared with placebo, IPE 4 g/day significantly reduced TG, non-high-density lipoprotein cholesterol, very-low-density lipoprotein cholesterol (VLDL-C), lipoprotein-associated phospholipase A2, apolipoprotein B (Apo B), total cholesterol, high-density lipoprotein cholesterol, VLDL-TG, oxidized LDL, and remnant-like particle cholesterol in all 3 diabetes groups, LDL-C in the total diabetes group, and hsCRP in the total and less-controlled diabetes groups. Decreases in hsCRP and Apo B were much greater in patients with less-controlled diabetes. There were no significant increases in fasting plasma glucose, A1c, insulin, or homeostasis model assessment-estimated insulin resistance in any group.ConclusionIPE 4 g/day significantly improved lipid and lipid-related parameters without worsening glycemic control in patients with diabetes and mixed dyslipidemia, with possibly greater effects among those with less-controlled diabetes.Trial registrationClinicaltrials.gov Identifier NCT01047501

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Section: Discussionsupporting

confidence: 91%

Effects of icosapent ethyl on lipid and inflammatory parameters in patients with diabetes mellitus-2, residual elevated triglycerides (200–500 mg/dL), and on statin therapy at LDL-C goal: the ANCHOR study

Brinton

Ballantyne

Bays

et al. 2013

Cardiovasc Diabetol

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“…However, data from models of prediabetes, namely the HSu-treated rat, are scarce [15,16]. Our study demonstrates no differences on glycemia in the fasting state, but a significant increase in the fed (postprandial) state in HSu-treated rats, together with impaired glucose tolerance, hyperinsulinemia and insulin resistance.…”

Section: Discussionmentioning

confidence: 44%

Early cardiac changes in a rat model of prediabetes: brain natriuretic peptide overexpression seems to be the best marker

Nunes

Soares

Fernandes

et al. 2013

Cardiovasc Diabetol

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BackgroundDiabetic cardiomyopathy (DCM) is defined as structural and functional changes in the myocardium due to metabolic and cellular abnormalities induced by diabetes mellitus (DM). The impact of prediabetic conditions on the cardiac tissue remains to be elucidated. The goal of this study was to elucidate whether cardiac dysfunction is already present in a state of prediabetes, in the presence of insulin resistance, and to unravel the underlying mechanisms, in a rat model without obesity and hypertension as confounding factors.MethodsTwo groups of 16-week-old Wistar rats were tested during a 9 week protocol: high sucrose (HSu) diet group (n = 7) – rats receiving 35% of sucrose in drinking water vs the vehicle control group (n = 7). The animal model was characterized in terms of body weight (BW) and the glycemic, insulinemic and lipidic profiles. The following parameters were assessed to evaluate possible early cardiac alterations and underlying mechanisms: blood pressure, heart rate, heart and left ventricle (LV) trophism indexes, as well as the serum and tissue protein and/or the mRNA expression of markers for fibrosis, hypertrophy, proliferation, apoptosis, angiogenesis, endothelial function, inflammation and oxidative stress.ResultsThe HSu-treated rats presented normal fasting plasma glucose (FPG) but impaired glucose tolerance (IGT), accompanied by hyperinsulinemia and insulin resistance (P < 0.01), confirming this rat model as prediabetic. Furthermore, although hypertriglyceridemia (P < 0.05) was observed, obesity and hypertension were absent. Regarding the impact of the HSu diet on the cardiac tissue, our results indicated that 9 weeks of treatment might be associated with initial cardiac changes, as suggested by the increased LV weight/BW ratio (P < 0.01) and a remarkable brain natriuretic peptide (BNP) mRNA overexpression (P < 0.01), together with a marked trend for an upregulation of other important mediators of fibrosis, hypertrophy, angiogenesis and endothelial lesions, as well as oxidative stress. The inflammatory and apoptotic markers measured were unchanged.ConclusionsThis animal model of prediabetes/insulin resistance could be an important tool to evaluate the early cardiac impact of dysmetabolism (hyperinsulinemia and impaired glucose tolerance with fasting normoglycemia), without confounding factors such as obesity and hypertension. Left ventricle hypertrophy is already present and brain natriuretic peptide seems to be the best early marker for this condition.

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“…4f). Notably, the detection of GLA in serum samples has previously been frequently missed 48–50 due to its low abundance or unanticipated presence during SRM-based targeted analysis.…”

Section: Resultsmentioning

confidence: 99%

Identification and Quantitation of Fatty Acid Double Bond Positional Isomers: A Shotgun Lipidomics Approach Using Charge-Switch Derivatization

Yang¹,

Dilthey²,

Gross

2013

Anal. Chem.

108

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The specific locations of double bonds in mammalian lipids have profound effects on biological membrane structure, dynamics and lipid second messenger production. Herein, we describe a shotgun lipidomics approach that exploits charge-switch derivatization with N-(4-aminomethylphenyl) pyridinium (AMPP) and tandem mass spectrometry for identification and quantification of fatty acid double bond positional isomers. Through charge-switch derivatization of fatty acids followed by positive-ion mode ionization and fragmentation analysis, a marked increase in analytic sensitivity (low fmol/μL) and the identification of double bond positional isomers can be obtained. Specifically, the locations of proximal double bonds in AMPP-derivatized fatty acids are identified by diagnostic fragment ions resulting from the markedly reduced 1,4-hydrogen elimination from the proximal olefinic carbons. Additional fragmentation patterns resulting from allylic cleavages further substantiated the double bond position assignments. Moreover, quantification of fatty acid double bond positional isomers is achieved by the linear relationship of the normalized intensities of characteristic fragment ions vs. the isomeric compositions of discrete fatty acid positional isomers. The application of this approach for the analysis of fatty acids in human serum demonstrated the existence of two double bond isomers of linolenic acid (i.e., Δ6,9,12 18:3, γ-linolenic acid (GLA), and Δ9,12,15 18:3, α-linolenic acid (ALA)). Remarkably, the isomeric ratio of GLA vs. ALA esterified in triglycerides was three-fold higher than the ratio of their non-esterified moieties. Through this developed method, previously underestimated or unidentified alterations in fatty acid structural isomers can be determined facilitating the identification of novel biomarkers and maladaptive alterations in lipid metabolism during disease.

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Reduction of n-3 PUFAs, specifically DHA and EPA, and enhancement of peroxisomal beta-oxidation in type 2 diabetic rat heart

Cited by 39 publications

References 35 publications

Effects of icosapent ethyl on lipid and inflammatory parameters in patients with diabetes mellitus-2, residual elevated triglycerides (200–500 mg/dL), and on statin therapy at LDL-C goal: the ANCHOR study

Effects of icosapent ethyl on lipid and inflammatory parameters in patients with diabetes mellitus-2, residual elevated triglycerides (200–500 mg/dL), and on statin therapy at LDL-C goal: the ANCHOR study

Early cardiac changes in a rat model of prediabetes: brain natriuretic peptide overexpression seems to be the best marker

Identification and Quantitation of Fatty Acid Double Bond Positional Isomers: A Shotgun Lipidomics Approach Using Charge-Switch Derivatization

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