Posts Tagged ‘prevent type 2 diabetes’

Omega-3 fatty acids attenuate constitutive and insulin-induced CD36 expression through a suppression of PPAR α/γ activity in microvascular endothelial cells.

Saturday, September 10th, 2011

Raffaele De Caterina, MD, PhD, Institute of Cardiology, “G. d’Annunzio” University – Chieti, C/o Ospedale SS. Annunziata, Via dei Vestini, 66013 Chieti, Italy, Tel: +39 0871 41512, Fax: +39 0871 553 461, E-mail: rdecater@unich.it.

Abstract

Microvascular dysfunction occurs in insulin resistance and/or hyperinsulinaemia. Enhanced uptake of free fatty acids (FFA) and oxidised low-density lipoproteins (oxLDL) may lead to oxidative stress and microvascular dysfunction interacting with CD36, a PPARα/γ-regulated scavenger receptor and long-chain FFA transporter. We investigated CD36 expression and CD36-mediated oxLDL uptake before and after insulin treatment in human dermal microvascular endothelial cells (HMVECs), ± different types of fatty acids (FA), including palmitic, oleic, linoleic, arachidonic, eicosapentaenoic (EPA), and docosahexaenoic (DHA) acids. Insulin (10⁻⁸ and 10⁻⁷ M) time-dependently increased DiI-oxLDL uptake and CD36 surface expression (by 30 ± 13%, p<0.05 vs. untreated control after 24 hours incubation), as assessed by ELISA and flow cytometry, an effect that was potentiated by the PI3-kinase inhibitor wortmannin and reverted by the ERK1/2 inhibitor PD98059 and the PPARα/γ antagonist GW9662. A ≥24 hour exposure to 50 μM DHA or EPA, but not other FA, blunted both the constitutive (by 23 ℜ∓ 3% and 29 ± 2%, respectively, p<0.05 for both) and insulin-induced CD36 expressions (by 45 ± 27 % and 12 ± 3 %, respectively, p<0.05 for both), along with insulin-induced uptake of DiI-oxLDL and the downregulation of phosphorylated endothelial nitric oxide synthase (P-eNOS). At gel shift assays, DHA reverted insulin-induced basal and oxLDL-stimulated transactivation of PPRE and DNA binding of PPARα/γ and NF-κB. In conclusion, omega-3 fatty acids blunt the increased CD36 expression and activity promoted by high concentrations of insulin. Such mechanisms may be the basis for the use of omega-3 fatty acids in diabetic microvasculopathy.

Omega 3 fish oil may help activate anti-diabetic genes

Tuesday, March 8th, 2011

Fish oils may help to activate anti-diabetic genes

Polyunsaturated fatty acid fish oils may activate genes that regulate fat cell differentiation and glucose homeostasis, according to new research on mice.

The new study published in Journal of Nutritional Biochemistry suggests supplementation with omega3 fish oil activates the transcription factor PPARγ, increasing regulation of adipocytes and helps to maintain glucose homeostasis.

“We demonstrated that adipogenic genes and glucose metabolism genes were elevated in PPARγ transgenic mice when fed fish oil. This transgenic mouse model provided direct evidence to demonstrate omega 3 , especially EPA  regulate glucose homeostasis through interaction with PPARγ,” wrote the researchers, led by Dr Yu-Hsiang Yu from the National Taiwan University

Vital roles

Peroxisome-proliferator-activated receptor γ (PPARγ) is considered an important transcription factor in regulating fat cell (adipocyte) differentiation, and is also known to play a vital role in maintaining glucose homeostasis. The transcription factor is a target for many anti-diabetic drugs as activation promotes glucose dispersal.

Activation of PPARγ occurs through the binding of specific ligand molecules; however, polyunsaturated fatty acids such as arachidonic acid, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are also known to have a high binding affinity for PPARγ.

Previous studies suggest that polyunsaturated fatty acids (PUFA) and their metabolites are able to regulate PPARγ activity, demonstrating that DHA treatment increases PPARγ-responsive gene expression in a cell model.

However, most research demonstrating PPARγ activity uses in vitro cell models and there is currently no direct evidence available to demonstrate that polyunsaturated fatty acids are able to activate PPARγ in vivo.

The authors said the current experiment was designed to determine the potential for PUFA, particularly EPA and DHA, to activate the function of PPARγ in vivo.

Wild-type and transgenic mice – with over expressed PPARγ –were supplemented with either fish oil or PPARγ ligands (rosiglitazone) for four months to investigate whether fish oils have similar effects to true PPARγ ligands in vivo.

Results

Dietary rosiglitazone fed mice had a significantly lower feed intake, but had no significant effect on body weight or fat pad weigh, whereas fish oil supplementation did not significantly decrease feed intake, but significantly decreased body and fat pad weight, found the researchers.

Dr. Yu and colleagues reported that adipogenic genes (LPL, FAT, SREBP-1c and FAS) were markedly up-regulated by rosiglitazone supplementation. Fish oil supplementation increased LPL and FAT, but not SREBP-1c or FAS; however, stained muscle sections indicated no lipid accumulation in skeletal muscle.

Researchers noted that transgenic mice fed a fish oil supplementation had increased expression of adipogenic and glucose uptake genes, leading to reduced plasma glucose concentration.

Natural regulator

The authors suggested that polyunsaturated fatty acids, particularly EPA and DHA, may serve as a natural regulator of glucose uptake in vivo, stating that such effects are mainly mediated through PPARγ activation.

“Our data demonstrated that the PPARγ-regulated glucose metabolism genes, GLUT-4 and ADN were dramatically increased in skeletal muscle of PPARγ transgenic mice when fed rosiglitazone or fish oil, suggesting activation … by either ligand,” concluded the authors.

Source: Journal of Nutritional Biochemistry

“The function of porcine PPARγ and dietary fish oil effect on the expression of lipid and glucose metabolism related genes”

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