Posts Tagged ‘omega3 and benefits to 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.

What is Diabetes

Monday, August 29th, 2011

Diabetes is a chronic disease that occurs either when the pancreas does not produce enough insulin or when the body cannot effectively use the insulin it produces. Insulin is a hormone that regulates blood sugar. Hyperglycaemia, or raised blood sugar, is a common effect of uncontrolled diabetes and over time leads to serious damage to many of the body’s systems, especially the nerves and blood vessels.
Type 1 diabetes (previously known as insulin-dependent, juvenile or childhood-onset) is characterized by deficient insulin production and requires daily administration of insulin. The cause of type 1 diabetes is not known and it is not preventable with current knowledge.

Symptoms include excessive excretion of urine (polyuria), thirst (polydipsia), constant hunger, weight loss, vision changes and fatigue. These symptoms may occur suddenly.
Type 2 diabetes (formerly called non-insulin-dependent or adult-onset) results from the body’s ineffective use of insulin. Type 2 diabetes comprises 90% of people with diabetes around the world, and is largely the result of excess body weight and physical inactivity.

Symptoms may be similar to those of Type 1 diabetes, but are often less marked. As a result, the disease may be diagnosed several years after onset, once complications have already arisen.

Until recently, this type of diabetes was seen only in adults but it is now also occurring in children.
Gestational diabetes is hyperglycaemia with onset or first recognition during pregnancy.

Symptoms of gestational diabetes are similar to Type 2 diabetes. Gestational diabetes is most often diagnosed through prenatal screening, rather than reported symptoms.

Impaired glucose tolerance (IGT) and impaired fasting glycaemia (IFG)
Impaired glucose tolerance (IGT) and impaired fasting glycaemia (IFG) are intermediate conditions in the transition between normality and diabetes. People with IGT or IFG are at high risk of progressing to type 2 diabetes, although this is not inevitable.

What are common consequences of diabetes?
Over time, diabetes can damage the heart, blood vessels, eyes, kidneys, and nerves.

Diabetes increases the risk of heart disease and stroke. 50% of people with diabetes die of cardiovascular disease (primarily heart disease and stroke).
Combined with reduced blood flow, neuropathy in the feet increases the chance of foot ulcers and eventual limb amputation.
Diabetic retinopathy is an important cause of blindness, and occurs as a result of long-term accumulated damage to the small blood vessels in the retina. After 15 years of diabetes, approximately 2% of people become blind, and about 10% develop severe visual impairment.
Diabetes is among the leading causes of kidney failure. 10-20% of people with diabetes die of kidney failure.
Diabetic neuropathy is damage to the nerves as a result of diabetes, and affects up to 50% of people with diabetes. Although many different problems can occur as a result of diabetic neuropathy, common symptoms are tingling, pain, numbness, or weakness in the feet and hands.

Omega 3 Fish Oil EPA and DHA reduce anxiety and inflammation in healthy students

Thursday, July 14th, 2011

Omega-3 Reduces Anxiety and Inflammation in Healthy Students,
A new study gauging the impact of consuming more fish oil showed a marked reduction both in inflammation and, surprisingly, in anxiety among a cohort of healthy young people.

The findings suggest that if young participants can get such improvements from specific dietary supplements, then the elderly and people at high risk for certain diseases might benefit even more.
The findings by a team of researchers at Ohio State University were just published in the journal Brain, Behavior and Immunity. It is the latest from more than three decades of research into links between psychological stress and immunity.
Omega-3 polyunsaturated fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have long been considered as positive additives to the diet. Earlier research suggested that the compounds might play a role in reducing the level of cytokines in the body, compounds that promote inflammation, and perhaps even reduce depression.
Psychological stress has repeatedly been shown to increase cytokine production so the researchers wondered if increasing omega-3 might mitigate that process, reducing inflammation.
To test their theory, they turned to a familiar group of research subjects — medical students. Some of the earliest work these scientists did showed that stress from important medical school tests lowered students’ immune status.
“We hypothesized that giving some students omega-3 supplements would decrease their production of proinflammatory cytokines, compared to other students who only received a placebo,” explained Janice Kiecolt-Glaser, professor of psychology and psychiatry.
“We thought the omega-3 would reduce the stress-induced increase in cytokines that normally arose from nervousness over the tests.”
The team assembled a field of 68 first- and second-year medical students who volunteered for the clinical trial. The students were randomly divided into six groups, all of which were interviewed six times during the study. At each visit, blood samples were drawn from the students who also completed a battery of psychological surveys intended to gauge their levels of stress, anxiety or depression. The students also completed questionnaires about their diets during the previous weeks.
Half the students received omega-3 supplements while the other half were given placebo pills.
“The supplement was probably about four or five times the amount of fish oil you’d get from a daily serving of salmon, for example,” explained Martha Belury, professor of human nutrition and co-author in the study.
Part of the study, however, didn’t go according to plans.
Changes in the medical curriculum and the distribution of major tests throughout the year, rather than during a tense three-day period as was done in the past, removed much of the stress that medical students had shown in past studies.
“These students were not anxious. They weren’t really stressed. They were actually sleeping well throughout this period, so we didn’t get the stress effect we had expected,” Kiecolt-Glaser said.
But the psychological surveys clearly showed an important change in anxiety among the students: Those receiving the omega-3 showed a 20 percent reduction in anxiety compared to the placebo group.
An analysis of the of the blood samples from the medical students showed similar important results.
“We took measurements of the cytokines in the blood serum, as well as measured the productivity of cells that produced two important cytokines, interleukin-6 (IL-6) and tumor necrosis factor alpha (TNFa),” said Ron Glaser, professor of molecular virology, immunology & medical genetics and director of the Institute for Behavioral Medicine Research.
“We saw a 14 percent reduction in the amounts of IL-6 among the students receiving the omega-3.” Since the cytokines foster inflammation, “anything we can do to reduce cytokines is a big plus in dealing with the overall health of people at risk for many diseases,” he said.
While inflammation is a natural immune response that helps the body heal, it also can play a harmful role in a host of diseases ranging from arthritis to heart disease to cancer.

Omega 3 fish oil benefits may prevent Diabetic retinopathy

Thursday, March 31st, 2011

RESEARCH ARTICLE
ANTI-ANGIOGENESIS
5-Lipoxygenase Metabolite 4-HDHA Is a Mediator of the Antiangiogenic Effect of ω-3 Polyunsaturated Fatty Acids
Przemyslaw Sapieha1,2,*, Andreas Stahl1,3,*, Jing Chen1, Molly R. Seaward1, Keirnan L. Willett1, Nathan M. Krah1, Roberta J. Dennison1, Kip M. Connor1,†, Christopher M. Aderman1, Elvira Liclican4, Arianna Carughi5,6, Dalia Perelman5,6, Yoshihide Kanaoka7, John Paul SanGiovanni8, Karsten Gronert4 and Lois E. H. Smith1,‡
+ Author Affiliations

1Department of Ophthalmology, Harvard Medical School, Children’s Hospital Boston, 300 Longwood Avenue, Boston, MA 02115, USA.
2Department of Ophthalmology, Maisonneuve-Rosemont Hospital Research Centre, University of Montreal, Montreal, Quebec, Canada H1T 2M4.
3University Eye Hospital Freiburg, Killianstrasse 5, Freiburg 79106, Germany.
4Vision Science Program, School of Optometry, University of California, Berkeley, CA 94720, USA.
5Health Research and Studies Center, Los Altos, CA 94022, USA.
6Palo Alto Medical Foundation, Palo Alto, CA 94301, USA.
7Department of Medicine, Harvard Medical School and Brigham and Women’s Hospital, Boston, MA 02115, USA.
8Division of Epidemiology and Clinical Research, National Eye Institute, Bethesda, MD 20892, USA
‡To whom correspondence should be addressed. E-mail: lois.smith@childrens.harvard.edu
ABSTRACT

Lipid signaling is dysregulated in many diseases with vascular pathology, including cancer, diabetic retinopathy, retinopathy of prematurity, and age-related macular degeneration. We have previously demonstrated that diets enriched in ω-3 polyunsaturated fatty acids (PUFAs) effectively reduce pathological retinal neovascularization in a mouse model of oxygen-induced retinopathy, in part through metabolic products that suppress microglial-derived tumor necrosis factor–α. To better understand the protective effects of ω-3 PUFAs, we examined the relative importance of major lipid metabolic pathways and their products in contributing to this effect. ω-3 PUFA diets were fed to four lines of mice deficient in each key lipid-processing enzyme (cyclooxygenase 1 or 2, or lipoxygenase 5 or 12/15), retinopathy was induced by oxygen exposure; only loss of 5-lipoxygenase (5-LOX) abrogated the protection against retinopathy of dietary ω-3 PUFAs. This protective effect was due to 5-LOX oxidation of the ω-3 PUFA lipid docosahexaenoic acid to 4-hydroxy-docosahexaenoic acid (4-HDHA). 4-HDHA directly inhibited endothelial cell proliferation and sprouting angiogenesis via peroxisome proliferator–activated receptor γ (PPARγ), independent of 4-HDHA’s anti-inflammatory effects. Our study suggests that ω-3 PUFAs may be profitably used as an alternative or supplement to current anti–vascular endothelial growth factor (VEGF) treatment for proliferative retinopathy and points to the therapeutic potential of ω-3 PUFAs and metabolites in other diseases of vasoproliferation. It also suggests that cyclooxygenase inhibitors such as aspirin and ibuprofen (but not lipoxygenase inhibitors such as zileuton) might be used without losing the beneficial effect of dietary ω-3 PUFA.

↵* These authors contributed equally to this work.
↵† Present address: Massachusetts Eye and Ear Infirmary, Angiogenesis Laboratory, Department of Ophthalmology, Harvard Medical School, 243 Charles Street, Boston, MA 02114, USA.
Citation: P. Sapieha, A. Stahl, J. Chen, M. R. Seaward, K. L. Willett, N. M. Krah, R. J. Dennison, K. M. Connor, C. M. Aderman, E. Liclican, A. Carughi, D. Perelman, Y. Kanaoka, J. P. SanGiovanni, K. Gronert, L. E. H. Smith, 5-Lipoxygenase Metabolite 4-HDHA Is a Mediator of the Antiangiogenic Effect of ω-3 Polyunsaturated Fatty Acids. Sci. Transl. Med. 3, 69ra12 (2011).

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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