Mechanisms of enhanced insulin secretion and sensitivity with n-3 unsaturated fatty acids

Bhaswant, Maharshi; Poudyal, Hemant; Brown, Lindsay

doi:10.1016/j.jnutbio.2015.02.001

Cited by 110 publications

(93 citation statements)

References 225 publications

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“…PPARs are activated by noncovalent binding of ligands which include n-3 LCPUFAs and various lipid mediators. DHA can induce and activate PPARs [53] and upregulate a number of PPAR target genes [54] , which may be at least partly responsible for the ability of DHA to lower fasting plasma triglyceride concentrations [55] , to increase insulin sensitivity [56] and to reduce inflammation [57] .…”

Section: Dha Can Act Via Cell Surface and Intracellular Receptorsmentioning

confidence: 99%

Docosahexaenoic Acid

2016

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Docosahexaenoic acid (DHA) is a long-chain, highly unsaturated omega-3 (n-3) fatty acid. It has a structure that gives it unique physical and functional properties. DHA is metabolically related to other n-3 fatty acids: it can be synthesised from the plant essential fatty acid α-linolenic acid (ALA). However, this pathway does not appear to be very efficient in many individuals, although the conversion of ALA to DHA is much better in young women than in young men. Furthermore, young infants may be more efficient converters of ALA to DHA than many adults, although the conversion rate is variable among infants. Many factors have been identified that affect the rate of conversion. The implication of poor conversion is that preformed DHA needs to be consumed. DHA is found in fairly high amounts in seafood, especially fatty fish, and in various forms of n-3 supplements. The amount of DHA in seafood and in supplements varies. Breast milk contains DHA. DHA is found esterified into complex lipids within the bloodstream, in adipose stores and in cell membranes. Its concentration in different compartments varies greatly. The brain and eye have high DHA contents compared to other organs. DHA is especially concentrated in the grey matter of the brain and in the rod outer segments of the retina. In the brain DHA is involved in neuronal signalling, while in the eye it is involved in the quality of vision. DHA is accumulated in the brain and eye late in pregnancy and in early infancy. A lower DHA content is linked to poorer cognitive development and visual function. DHA affects cell and tissue physiology and function through numerous mechanisms, including alterations in membrane structure and function, in membrane protein function, in cellular signalling and in lipid mediator production.

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Section: Dha Can Act Via Cell Surface and Intracellular Receptorsmentioning

confidence: 99%

Docosahexaenoic Acid

2016

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“…Epidemiological studies and meta-analyses indicate that dietary modifications that increase the relative abundance of dietary n-3 polyunsaturated fatty acids (PUFA), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid, can reduce the risks of DM as well as CAD [3–5] Most animal experiments also document beneficial effects of n-3 PUFA on insulin sensitivity, secretion, and glucose metabolism under condition of obesity, insulin resistance and DM [6, 7]. These findings suggest that n-3 PUFA may help control and prevent DM possibly due to improvement of insulin secretion and sensitivity.…”

Section: Introductionmentioning

confidence: 99%

Effects of 6-month eicosapentaenoic acid treatment on postprandial hyperglycemia, hyperlipidemia, insulin secretion ability, and concomitant endothelial dysfunction among newly-diagnosed impaired glucose metabolism patients with coronary artery disease. An open label, single blinded, prospective randomized controlled trial

Sawada

Tsubata

Hashimoto³

et al. 2016

Cardiovasc Diabetol

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BackgroundRecent experimental studies have revealed that n-3 fatty acids, such as eicosapentaenoic acid (EPA) regulate postprandial insulin secretion, and correct postprandial glucose and lipid abnormalities. However, the effects of 6-month EPA treatment on postprandial hyperglycemia and hyperlipidemia, insulin secretion, and concomitant endothelial dysfunction remain unknown in patients with impaired glucose metabolism (IGM) and coronary artery disease (CAD).Methods and resultsWe randomized 107 newly diagnosed IGM patients with CAD to receive either 1800 mg/day of EPA (EPA group, n = 53) or no EPA (n = 54). Cookie meal testing (carbohydrates: 75 g, fat: 28.5 g) and endothelial function testing using fasting-state flow-mediated dilatation (FMD) were performed before and after 6 months of treatment. The primary outcome of this study was changes in postprandial glycemic and triglyceridemic control and secondary outcomes were improvement of insulin secretion and endothelial dysfunction. After 6 months, the EPA group exhibited significant improvements in EPA/arachidonic acid, fasting triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C). The EPA group also exhibited significant decreases in the incremental TG peak, area under the curve (AUC) for postprandial TG, incremental glucose peak, AUC for postprandial glucose, and improvements in glycometabolism categorization. No significant changes were observed for hemoglobin A1c and fasting plasma glucose levels. The EPA group exhibited a significant increase in AUC-immune reactive insulin/AUC-plasma glucose ratio (which indicates postprandial insulin secretory ability) and significant improvements in FMD. Multiple regression analysis revealed that decreases in the TG/HDL-C ratio and incremental TG peak were independent predictors of FMD improvement in the EPA group.ConclusionsEPA corrected postprandial hypertriglyceridemia, hyperglycemia and insulin secretion ability. This amelioration of several metabolic abnormalities was accompanied by recovery of concomitant endothelial dysfunction in newly diagnosed IGM patients with CAD.Clinical Trial Registration UMIN Registry number: UMIN000011265 (https://www.upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&recptno=R000013200&language=E)Electronic supplementary materialThe online version of this article (doi:10.1186/s12933-016-0437-y) contains supplementary material, which is available to authorized users.

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“…Recent studies suggest that the actual levels of some of these proteins may also be reduced resulting from new juxtaposition to lysosomes and proteasomes [18]. Additional mechanisms include reduced adhesion molecule expression and motility and improved insulin sensitivity [20,21]. A sum result is likely reduction in proliferation, increased apoptosis, and reduced mammary carcinogenesis [18,19,22].…”

Section: Introductionmentioning

confidence: 99%

Modulation of Breast Cancer Risk Biomarkers by High-Dose Omega-3 Fatty Acids: Phase II Pilot Study in Postmenopausal Women

Fabian

Kimler

Phillips

et al. 2015

Cancer Prevention Research

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Higher intakes of the omega-3 eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) relative to the omega-6 arachidonic acid (AA) have been variably associated with reduced risk of premenopausal breast cancer. The purpose of this pilot trial was to assess feasibility and explore effects of high dose EPA and DHA on blood and benign breast tissue risk biomarkers prior to design of a placebo controlled Phase IIB trial. Premenopausal women with evidence of hyperplasia +/- atypia by baseline random periareolar fine needle aspiration (RPFNA) were given 1860 mg of EPA + 1500 mg of DHA ethyl esters daily for 6 months. Blood and benign breast tissue were sampled during the same menstrual cycle phase pre-study and a median of 3 weeks after last dose. Additional blood was obtained within 24 hours of last dose. Feasibility which was pre-defined as 50% uptake, 85% retention and 70% compliance, was demonstrated with 46% uptake, 94% completion, and 85% compliance. Cytologic atypia decreased from 77 to 38% (p=0.002), and Ki-67 from a median of 2.1 to 1.0 % (p=0.021) with an increase in the ratio of EPA + DHA to AA in erythrocyte phospholipids but no change in blood hormones, adipokines, or cytokines. Exploratory breast proteomics assessment showed decreases in several proteins involved in hormone and cytokine signaling with mixed effects on those in the AKT/mTOR pathways. Further investigation of EPA plus DHA for breast cancer prevention in a placebo controlled trial in premenopausal women is warranted.

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Mechanisms of enhanced insulin secretion and sensitivity with n-3 unsaturated fatty acids

Cited by 110 publications

References 225 publications

Docosahexaenoic Acid

Docosahexaenoic Acid

Modulation of Breast Cancer Risk Biomarkers by High-Dose Omega-3 Fatty Acids: Phase II Pilot Study in Postmenopausal Women

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