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

The new study published in Journal of Nutritional Biochemistry ​suggests supplementation with fish oils 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 PUFA, especially EPA and DHA, 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​

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

“The function of porcine PPARγ 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