linoleic-acid and glyceryl-2-arachidonate

Dietary intake of linoleic acid (LNA, 18:2n-6) has increased dramatically during the 20th century and is associated with greater prevalence of obesity. The endocannabinoid system is involved in regulation of energy balance and a sustained hyperactivity of the endocannabinoid system may contribute to obesity. Arachidonic acid (ARA, 20:4n-6) is the precursor for 2-AG and anandamide (AEA), and we sought to determine if low fat diets (LFD) could be made obesogenic by increasing the endocannabinoid precursor pool of ARA, causing excessive endocannabinoid signaling leading to weight gain and a metabolic profile associated with obesity. Mice (C57BL/6j, 6 weeks of age) were fed 1 en% LNA and 8 en% LNA in low fat (12.5 en%) and medium fat diets (MFD, 35 en%) for 16 weeks. We found that increasing dietary LNA from 1 to 8 en% in LFD and MFD significantly increased ARA in phospholipids (ARA-PL), elevated 2-AG and AEA in liver, elevated plasma leptin, and resulted in larger adipocytes and more macrophage infiltration in adipose tissue. In LFD, dietary LNA of 8 en% increased feed efficiency and caused greater weight gain than in an isocaloric reduction to 1 en% LNA. Increasing dietary LNA from 1 to 8 en% elevates liver endocannabinoid levels and increases the risk of developing obesity. Thus a high dietary content of LNA (8 en%) increases the adipogenic properties of a low fat diet.

Topics: Adipose Tissue; Analysis of Variance; Animals; Arachidonic Acids; Body Weight; Diet; Diet, Fat-Restricted; Endocannabinoids; Erythrocytes; Fatty Acids; Glycerides; Leptin; Linoleic Acid; Liver; Macrophages; Male; Mice; Mice, Inbred C57BL; Obesity; Phospholipids; Polyunsaturated Alkamides; Risk Factors; Weight Gain

Neural stem cells express cannabinoid CB1 and CB2 receptors and the enzymes for the biosynthesis and metabolism of endocannabinoids (eCBs). Here we have studied the role of neural stem cell-derived eCBs as autonomous regulatory factors during differentiation. First, we examined the effect of an indirect eCB precursor linoleic acid (LA), a major dietary omega-6 fatty acid, on the eCB system in neural stem/progenitor cells (NSPCs) cultured in DMEM/F12 supplemented with N2 (N2/DF) as monolayer cells. LA upregulated eCB system-related genes and 2-arachidonoylglycerol (2-AG), but not anandamide (AEA), levels. Glial fibrillary acidic protein (GFAP) was significantly higher under LA-enriched conditions, and this effect was inhibited by the cannabinoid receptor type-1 (CB1) antagonist AM251. Second, the levels of AEA and 2-AG, as well as of the mRNA of eCB system-related genes, were measured in NSPCs after γ-aminobutyric acid (GABA) treatment. GABA upregulated AEA levels significantly in LA-enriched cultures and increased the mRNA expression of the 2-AG-degrading enzyme monoacylglycerol lipase. These effects of GABA were reproduced under culture conditions using neurobasal media supplemented with B27, which is commonly used for neurosphere culture. GABA stimulated astroglial differentiation in this medium as indicated by increased GFAP levels. This effect was abolished by AM251, suggesting the involvement of AEA and CB1 in GABA-induced astrogliogenesis. This study highlights the importance of eCB biosynthesis and CB1 signalling in the autonomous regulation of NSPCs and the influence of the eCB system on astrogliogenesis induced by nutritional factors or neurotransmitters, such as LA and GABA.

Topics: Acetyltransferases; Analysis of Variance; Animals; Arachidonic Acids; Astrocytes; Cell Differentiation; Cells, Cultured; Endocannabinoids; gamma-Aminobutyric Acid; Glial Fibrillary Acidic Protein; Glycerides; Linoleic Acid; Mass Spectrometry; Mice; Neural Stem Cells; Piperidines; Polyunsaturated Alkamides; Pyrazoles; RNA, Messenger; Up-Regulation

Conjugated linoleic acid (CLA) has a role of biogenic regulation through modifying prostaglandin production. However, its effects on related metabolites of arachidonate remain unclear. Therefore, the effects of CLA on brain endocannabinoid content as well as its analogs were investigated. Mice (3-week-old), provided with diets containing 3% linoleic acid or 3% CLA for 4 weeks, were sacrificed and lipids were extracted from their cerebral cortex and hypothalamus. The amounts of N-arachidonoyl-ethanolamide, 2-arachidonoyl-glycerol (2-AG), oleoyl-ethanolamide and palmitoyl-ethanolamide were determined quantitatively by LC-MS. The 2-AG level in the cerebral cortex was significantly decreased by CLA treatment, but the other compounds were unaffected in the cerebral cortex and hypothalamus. The present study indicated that dietary CLA site-selectively decreases 2-AG in the cerebral cortex.

Topics: Administration, Oral; Animals; Arachidonic Acids; Cannabinoid Receptor Modulators; Cerebral Cortex; Endocannabinoids; Glycerides; Hypothalamus; Linoleic Acid; Linoleic Acids, Conjugated; Mice