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Differential modulation of white adipose tissue endocannabinoid levels by n-3 fatty acids in obese mice and type 2 diabetic patients
M. Rossmeisl, J. Pavlisova, P. Janovska, O. Kuda, K. Bardova, J. Hansikova, M. Svobodova, M. Oseeva, J. Veleba, J. Kopecky, P. Zacek, E. Fiserova, T. Pelikanova, J. Kopecky,
Language English Country Netherlands
Document type Journal Article, Research Support, Non-U.S. Gov't
Grant support
NV15-27431A
MZ0
CEP Register
- MeSH
- Adipose Tissue, White metabolism MeSH
- Diabetes Mellitus, Type 2 blood diet therapy metabolism MeSH
- Diet, High-Fat adverse effects MeSH
- Adult MeSH
- Endocannabinoids blood metabolism MeSH
- Glucose metabolism MeSH
- Blood Glucose MeSH
- Middle Aged MeSH
- Humans MeSH
- Disease Models, Animal MeSH
- Mice, Inbred C57BL MeSH
- Mice, Obese MeSH
- Mice MeSH
- Obesity blood diet therapy etiology metabolism MeSH
- Fatty Acids, Omega-3 administration & dosage MeSH
- Dietary Supplements * MeSH
- Randomized Controlled Trials as Topic MeSH
- Aged MeSH
- Body Weight MeSH
- Treatment Outcome MeSH
- Animals MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Mice MeSH
- Aged MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
n-3 polyunsaturated fatty acids (n-3 PUFA) might regulate metabolism by lowering endocannabinoid levels. We examined time-dependent changes in adipose tissue levels of endocannabinoids as well as in parameters of glucose homeostasis induced by n-3 PUFA in dietary-obese mice, and compared these results with the effect of n-3 PUFA intervention in type 2 diabetic (T2DM) subjects. Male C57BL/6J mice were fed for 8, 16 or 24 weeks a high-fat diet alone (cHF) or supplemented with n-3 PUFA (cHF + F). Overweight/obese, T2DM patients on metformin therapy were given for 24 weeks corn oil (Placebo; 5 g/day) or n-3 PUFA concentrate as above (Omega-3; 5 g/day). Endocannabinoids were measured by liquid chromatography-tandem mass-spectrometry. Compared to cHF-fed controls, the cHF + F mice consistently reduced 2-arachidonoylglycerol (up to ~2-fold at week 24) and anandamide (~2-fold) in adipose tissue, while the levels of endocannabinoid-related anti-inflammatory molecules N-eicosapentaenoyl ethanolamine (EPEA) and N-docosahexaenoyl ethanolamine (DHEA) increased more than ~10-fold and ~8-fold, respectively. At week 24, the cHF + F mice improved glucose tolerance and fasting blood glucose, the latter being positively correlated with adipose 2-arachidonoylglycerol levels only in obese cHF-fed controls, like fasting insulin and HOMA-IR. In the patients, n-3 PUFA failed to reduce 2-arachidonoylglycerol and anandamide levels in adipose tissue and serum, but they increased both adipose tissue and serum levels of EPEA and DHEA. In conclusion, the inability of n-3 PUFA to reduce adipose tissue and serum levels of classical endocannabinoids might contribute to a lack of beneficial effects of these lipids on glucose homeostasis in T2DM patients.
Diabetes Centre Institute for Clinical and Experimental Medicine Prague Czech Republic
International Clinical Research Center St Anne's University Hospital Brno Brno Czech Republic
Proteomics Core Facility Faculty of Science Charles University Division BIOCEV Vestec Czech Republic
References provided by Crossref.org
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