Leta i den här bloggen

onsdag 25 maj 2016

DHA ja endokannabinoidi systeemi

 PubMed haku anta 19 vastausta , josita tuoreimmat otan sitaattina 25.5. 2016. 

Dyall SC, Mandhair HK, Fincham RE, Kerr DM, Roche M, Molina-Holgado F.
Neuropharmacology. 2016 Apr 1;107:387-395. doi: 10.1016/j.neuropharm.2016.03.055. [Epub ahead of print]
Emerging evidence suggests a complex interplay between the endocannabinoid system, omega-3 fatty acids and the immune system in the promotion of brain self-repair. However, it is unknown if all omega-3 fatty acids elicit similar effects on adult neurogenesis and if such effects are mediated or regulated by interactions with the endocannabinoid system. This study investigated the effects of DHA and EPA on neural stem cell (NSC) fate and the role of the endocannabinoid signalling pathways in these effects.
 EPA, but not DHA, significantly increased proliferation of NSCs compared to controls, an effect associated with enhanced levels of the endocannabinoid 2-arachidonylglycerol (2-AG) and p-p38 MAPK, effects attenuated by pre-treatment with CB1 (AM251) or CB2 (AM630) receptor antagonists.
 Furthermore, in NSCs derived from IL-1β deficient mice, EPA significantly decreased proliferation and p-p38 MAPK levels compared to controls, suggesting a key role for IL-1β signalling in the effects observed. Although DHA similarly increased 2-AG levels in wild-type NSCs, there was no concomitant increase in proliferation or p-p38 MAPK activity.
 In addition, in NSCs from IL-1β deficient mice, DHA significantly increased proliferation without effects on p-P38 MAPK, suggesting effects of DHA are mediated via alternative signalling pathways. 
These results provide crucial new insights into the divergent effects of EPA and DHA in regulating NSC proliferation and the pathways involved, and highlight the therapeutic potential of their interplay with endocannabinoid signalling in brain repair.
Simopoulos AP.
Nutrients. 2016 Mar 2;8(3). pii: E128. doi: 10.3390/nu8030128. Review.
In the past three decades, total fat and saturated fat intake as a percentage of total calories has continuously decreased in Western diets, while the intake of omega-6 fatty acid increased and the omega-3 fatty acid decreased, resulting in a large increase in the omega-6/omega-3 ratio from 1:1 during evolution to 20:1 today or even higher. This change in the composition of fatty acids parallels a significant increase in the prevalence of overweight and obesity. Experimental studies have suggested that omega-6 and omega-3 fatty acids elicit divergent effects on body fat gain through mechanisms of adipogenesis, browning of adipose tissue, lipid homeostasis, brain-gut-adipose tissue axis, and most importantly systemic inflammation. Prospective studies clearly show an increase in the risk of obesity as the level of omega-6 fatty acids and the omega-6/omega-3 ratio increase in red blood cell (RBC) membrane phospholipids, whereas high omega-3 RBC membrane phospholipids decrease the risk of obesity. Recent studies in humans show that in addition to absolute amounts of omega-6 and omega-3 fatty acid intake, the omega-6/omega-3 ratio plays an important role in increasing the development of obesity via both AA eicosanoid metabolites and hyperactivity of the cannabinoid system, which can be reversed with increased intake of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). A balanced omega-6/omega-3 ratio is important for health and in the prevention and management of obesity. 
Adibfar A, Saleem M, Lanctot KL, Herrmann N.
Curr Mol Med. 2016;16(2):137-64.
Depression, the most common mood disorder, is a leading contributor to the global burden of disease affecting more than 120 million individuals worldwide. Various pathophysiological processes underlie depression; this complexity renders it difficult to identify clinically useful diagnostic and prognostic markers, as well as treatment options. The current state of knowledge driving the management and treatment of depression remains incomplete, which underscores the need for further insight into pathways relevant to depression. Exploring co-morbid conditions, such as coronary artery disease, may be useful to further elucidate the etiopathology of depression. The present review therefore systematically identifies and critically evaluates relevant markers of depression as assessed in a high-risk population, namely patients with coronary artery disease. Biomarkers related to hypothalamicpituitary- adrenal axis dysregulation, inflammation, endothelial dysfunction, platelet activation and aggregation, serotonin activity, sympathetic nervous system activation, thyroid function, structural and morphological brain abnormalities, genetic variation, lipid metabolism, one-carbon metabolism, endocannabinoid signalling irregularities, and vitamin D deficiency are reviewed. Markers exhibiting the most consistent associations with depression include tumour necrosis factor-α, flow-mediated dilation, endothelin-1, endothelial progenitor cells, brain-derived neurotrophic factor, and docosahexaenoic acid. Further investigating the mechanisms underlying those markers and exploring novel pathways, such as oxidative stress, will extend the current state of knowledge and potentially lead to the identification of novel therapeutic targets.
Kim J, Carlson ME, Kuchel GA, Newman JW, Watkins BA.
Int J Obes (Lond). 2016 Jan;40(1):129-37. doi: 10.1038/ijo.2015.135. Epub 2015 Jul 29.
Naughton SS, Mathai ML, Hryciw DH, McAinch AJ.
Int J Endocrinol. 2013;2013:361895. doi: 10.1155/2013/361895. Epub 2013 May 26.
Meijerink J, Balvers M, Witkamp R.
Br J Pharmacol. 2013 Jun;169(4):772-83. doi: 10.1111/bph.12030. Review.

N-3 Long-chain polyunsaturated fatty acids (n-3 LC-PUFAs), in particular α-linolenic acid (18:3n-3), eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3) are receiving much attention because of their presumed beneficial health effects. To explain these, a variety of mechanisms have been proposed, but their interactions with the endocannabinoid system have received relatively little attention so far. However, it has already been shown some time ago that consumption of n-3 LC-PUFAs not only affects the synthesis of prototypic endocannabinoids like anandamide but also stimulates the formation of specific n-3 LC-PUFA-derived conjugates with ethanolamine, dopamine, serotonin or other amines. Some of these fatty amides show overlapping biological activities with those of typical endocannabinoids, whereas others possess distinct and sometimes largely unknown receptor affinities and other properties. The ethanolamine and dopamine conjugates of DHA have been the most investigated thus far. These mediators may provide promising new leads to the field of inflammatory and neurological disorders and for other pharmacological applications, including their use as carrier molecules for neurotransmitters to target the brain. Furthermore, combinations of n-3 LC-PUFA-derived fatty acid amides, their precursors and FAAH inhibitors offer possibilities to optimise their effects in health and disease.Free PMC Article

Inga kommentarer:

Skicka en kommentar