Details

Autor(en) / Beteiligte

• Rossmeisl, Martin
• Pavlisova, Jana
• Janovska, Petra
• Kuda, Ondrej
• Bardova, Kristina
• Hansikova, Jana
• Svobodova, Michaela
• Oseeva, Marina
• Veleba, Jiri
• Kopecky, Jan
• Zacek, Petr
• Fiserova, Eva
• Pelikanova, Terezie

Titel

Differential modulation of white adipose tissue endocannabinoid levels by n-3 fatty acids in obese mice and type 2 diabetic patients

Ist Teil von

• Biochimica et biophysica acta. Molecular and cell biology of lipids, 2018-07, Vol.1863 (7), p.712-725

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2018

Quelle

Access via ScienceDirect (Elsevier)

Beschreibungen/Notizen

• 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. [Display omitted] •Effect of n-3 PUFA on adipose tissue (WAT) endocannabinoid levels was investigated.•24-week-intervention was performed in obese mice and type 2 diabetic patients.•n-3 PUFA decreased WAT levels of 2-AG and AEA in mice but not in patients.•n-3 PUFA elevated EPEA and DHEA levels in WAT of both mice and patients.•Only in mice, n-3 PUFA improved glucose metabolism in concert with decreased 2-AG.