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Thursday, 10/28/2010 9:54:43 AM

Thursday, October 28, 2010 9:54:43 AM

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Fish oils may help to activate anti-diabetic genes: Study

By Nathan Gray, 25-Oct-2010

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 fish oils activates the transcription factor PPAR?, increasing regulation of adipocytes and helps to maintain glucose homeostasis.

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

Vital roles

Peroxisome-proliferator-activated receptor ? (PPAR?) 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 PPAR? 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 PPAR?.

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

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

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

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

Source: Journal of Nutritional Biochemistry

Published online ahead of print, doi: 10.1016/j.jnutbio.2010.01.006

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

Authors: Y.H. Yu, S.C. Wu, W.T.K. Cheng, H.J. Mersmann, T.L. Shen, S.T. Ding

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