Lee Swanson Research Update

Fish Oils Help Activate Anti-Diabetic Genes

November 2010

A new study involving mice reports that polyunsaturated fatty acid fish oils may activate genes that regulate fat cell differentiation and glucose homeostasis.

The study, published in the Journal of Nutritional Biochemistry, suggests supplementation with fish oils activates the transcription factor PPARy, increasing regulation of adipocytes and helps to maintain glucose homeostasis (blood glucose regulation).

PPARs (peroxisome-proliferator-activated receptors) are nuclear receptors that control many cellular and metabolic processes in the body.

"We demonstrated that adipogenic genes and glucose metabolism genes were elevated in PPARy transgenic mice when fed fish oil. This transgenic mouse model provided direct evidence to demonstrate Polyunsaturated Fatty Acids (PUFAs), especially EPA and DHA, regulate glucose homeostasis through interaction with PPARy," wrote the researchers, led by Dr. Yu-Hsiang Yu from the National Taiwan university.

PPARy 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 PPARy occurs through the binding of specific ligand molecules; however, polyunsaturated fatty acids such as arachidonic acid, eicosapentaenoic acid and docosahexaenoic acid are also known to have a high-binding affinity for PPARy.

Previous studies suggest that PUFAs and their metabolites are able to regulate PPARy activity, demonstrating that DHA treatment increases PPARy-responsive gene expression in a cell model.

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

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

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

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

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.

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 PPARy activation.

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

Journal of Nutritional Biochemistry Published online ahead of print.

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