Treatment of edema by joy

In my last post I discussed the Romantic Love Diet. For those who lost weight via this method the following post is redundant. For the rest the post adds support to my over-riding concept that having lots of joy is vital to long term weight loss.

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Activation of PPAR-alpha peripherally helps relieve edema. (1) indicates that increasing brain palmitoylethanolamide (PEA) can activate PPAR-alpha peripherally.

(2) indicates that human fat cells produce PEA in quantity. Suggesting that as a person drops weight they produce less PEA and may become more prone to edema.

Egg yolk has the highest concentration of PEA in commonly eaten foods. However, very little, if any, PEA is absorbed from our diet. And what is absorbed does not normally make it into our brains. (Yes, I have links to support these statements.)

So what is a swollen girl to do? Have fun! And LOTS of it. (3) points out the role being engrossed in life and love has in elevating brain PEA.

Maintaining weight loss is very few people can do it since it naturally leads to depression due to lowering of PEA. Which is relieved by eating lots of junk food. For the less than 5% of dieters who do restrict calories long term they normally accumulate water weight - particularly if they are female. If depression can't get them then misery at not dropping weight due to water retention probably will. The fix for people who wish to maintain weight loss is to live a more joyful life.

1. J Pharmacol Exp Ther. 2007 Jun 12
Acute intracerebroventricular administration of palmitoylethanolamide, an endogenous PPAR-{alpha} agonist, modulates carrageenan-induced paw edema in mice.
D'Agostino G, La Rana G, Russo R, Sasso O, Iacono A, Esposito E, Mattace Raso G, Cuzzocrea S, Lo Verme J, Piomelli D, Meli R, Calignano A.
Dept Exp Pharmacol University Naples Federico II.
Peroxisome proliferator-activated receptor alpha (PPAR-alpha) is a nuclear transcription factor. Although the presence of this receptor in different areas of CNS has been reported, its role remains unclear. Palmitoylethanolamide (PEA), a member of the fatty-acid ethanolamide family, acts peripherally as an endogenous PPAR-alpha ligand, exerting analgesic and anti-inflammatory effects. High levels of PEA in the CNS have been found, but the specific function of this lipid remains to be clarified. Using carrageenan-induced paw edema in mice, here we show that i.c.v. administration of PEA may control peripheral inflammation through central PPAR-alpha activation. A single i.c.v. administration of PEA (0.01-1microg), 30 min before carrageenan injection, reduced edema formation in the mouse carrageenan test. This effect was mimicked by GW7647 (0.01-1microg), a synthetic PPAR-alpha agonist. Moreover, central PEA administration significantly reduced the expression of the proinflammatory enzymes COX-2 and iNOS and significantly restored carrageenan-induced PPAR-alpha reduction in the spinal cord. To investigate the mechanism by which i.c.v. PEA attenuated the development of carrageenan-induced paw edema, we evaluated IkB-alpha degradation and NF-kB p65 activation in the cytosolic or nuclear extracts from spinal cord tissue. PEA prevented IkB-alpha degradation and NF-kB nuclear translocation confirming the involvement of this transcriptional factor in the control of peripheral inflammation. The obligatory role of PPAR-alpha in mediating PEA's effects was confirmed by the lack of the compounds anti-inflammatory effects in mutant mice lacking PPAR-alpha. In conclusion, our data show for the first time that PPAR-alpha activation in the CNS can control peripheral inflammation.
PMID: 17565008

2. http://www.obesityresearch.org/cgi/content/abstract/15/4/837
Obesity 15:837-845 (2007)
...N-palmitoylethanolamine is the most abundant cannabimimetic compound produced by human adipocytes, and its levels are significantly down-regulated by leptin but not affected by adiponectin and PPAR- agonist ciglitazone. N-palmitoylethanolamine itself does not affect either leptin or adiponectin secretion or PPAR- protein expression in adipocytes.

Discussion: This study has led to the identification of human adipocytes as a new source of endocannabinoids and related compounds. The biological significance of these adipocyte cannabimimetic compounds and their potential implication in obesity should deserve further investigations.

3. http://www.nutraplanet.com/product/1057/pea.html
PEA is a naturally occurring substance found in such items as blue-green algae, salami, bologna, and of course, chocolate. In recent years, it has also become an extremely popular ingredient in numerous dietary supplements, ranging from weight loss products to ‘whole health’ products.

Often dubbed “The love molecule” PEA, is a compound naturally produced by the brain, is responsible for the feeling of experiences associated with pleasure and mental awareness. For example, when one is absorbed by an activity like painting, sculpting, or reading a fascinating book, when the world around seems suspended and nothing can disturb us, when worries vanish and hunger goes away, in such moments PEA is being produced by the brain. Likewise, PEA is released in the brain when one experiences the feelings of love and joy. For this reason, PEA has been coined “The love molecule.” When taken orally, PEA is known to readily cross the blood-brain barrier and become immediately available in the brain.

In the brain, PEA is believed to act by having a greater affinity for the re-uptake mechanism for dopamine in presynaptic vesicles. Therefore, when present in the brain, PEA is captured into the presynaptic vesicles and occupies the space normally taken by dopamine. This leads to an increase in free-circulating dopamine in the presynaptic terminal and a higher concentration of dopamine diffusing into the synaptic cleft, therefore enhancing dopaminergic transmission.

This ability to modulate dopaminergic transmission provides PEA with interesting properties in increasing concentration and elevating mood.

PEA has also been shown to enhance norepinephrine transmission in the brain. Norepinephrine is also involved in the experience of joy. Enhancing norepinephrine transmission in the brain increases the experience of joy and reduces appetite. For example, if an animal is implanted with an electrode in an area of the brain concentrated in norepinephrine, and this electrode is activated by a pedal that the animal has access to, the animal will disregard food and water and will press the pedal relentlessly until exhaustion to elicit an electrical impulse in this area of the brain.

Finally, PEA also carries another interesting benefit. As mentioned before, PEA is produced by the brain when one is fully absorbed into an activity like painting, sculpting or reading a fascinating book. At such a time, the world seems to disappear around us, and we are no longer hungry. This phenomenon is not an anorectic effect in which hunger completely disappears but happens because our attention is taken away from the feeling of hunger. In this manner, PEA acts as an appetite suppressant. Therefore, through its ability to reduce appetite, PEA is an effective supplement to be taken as part of a comprehensive weight-loss program.


Nerissa