Anti-inflammatory Octopus

I always envied the neurophysiologists who studied the giant axons of lobster, because they could always eat their failed experiments. I was working on a fungal disease of soybeans. It had no gourmet prospects. My revenge came decades later, when I took a “research” trip to Tuscany to study the impact of Mediterranean cuisine on inflammation. Fish, cephalopods, red wine and tiramisu were my test materials and I was the test organism. For a month, I felt no stress, no inflammation and no pain. Recent research articles support my subjective conclusion that seafood and red wine from Siena to Venice are anti-inflammatory.

Recent tests of the fatty acid composition of Mediterranean fish and octopus show that the ratio of omega-3 to omega-6 fatty acids in the fish and octopus is roughly 2:1. (In contrast, the US ratio is 1:20) The omega-7 fatty acid, palmitoleic acid, which appears to act as an anti-inflammatory hormone, was also present. The prominent place of seafood in the Mediterranean diet and the high omega-3-rich fatty acid composition of that seafood, combined with the absence of the inflammatory, omega-6-rich vegetable oils, corn, soy, safflower, of the inflammatory US dietand the use of olive oil, go a long way to explain the relatively low incidence of inflammatory diseases in people who eat a Mediterranean diet. Just add some sunshine and exercise, and you will live better and longer.

Oh, by the way, the tiramisu was my daughters’ project to evaluate local variation of that dessert throughout Italy. So we ate tiramisu at a different restaurant each day for a month. The differences were amazing and the best tiramisu in Italy is ...

But the bottom line is the same. The Mediterranean diet is nothing more than another variant of the anti-inflammatory diet and lifestyle that I have been discussing throughout this blog. Biomedical research says that the US diet is killing us. You can go to Tuscany or you can just shop, cook and live wisely wherever you are.

references:
Ozogul Y, Ozogul F, Cicek E, Polat A, Kuley E. 2008. Fat content and fatty acid compositions of 34 marine water fish species from the Mediterranean Sea. Int J Food Sci Nutr. Oct 29:1-12.

Ben-Youssef S, Selmi S, Ezzeddine-Najai S, Sadok S. 2008. Total lipids and fatty acids composition of the coastal and the deep-sea common octopus (Octopus vulgaris) populations: a comparative study. Nutr Health. 19(3):195-201.

Palmitoleate: omega-7 lipokine

Palmitoleic acid is responsible for keeping people healthy (lipokine) and for the smell of old people (nonenal). Overproduction of this lipid by blocking uptake of fats results in resistance to type II diabetes and atherosclerosis.

If you listen to the commercials on television, you know that there are two sources of fats/cholesterol; you either make it in your cells or take from your diet. Recent research shows that mice that have been genetically modified to lack cytoplasmic lipid carriers, can’t store dietary fat, so they make more of their own lipids. Specifically, they make more palmitoleic acid (C16:1n7). By U.S. standards, those defective mice are very healthy. It turns out that palmitoleic acid acts as a lipid hormone that communicates between fat tissue and other organs, and maintains a healthy metabolic balance.

Lipids are hydrophobic and require protein carriers to be moved from their source, such as the intestines, through the blood and to be offloaded into tissues. Most of the lipids enter the diet as triglycerides, i.e. a three carbon glycerol with three fatty acids attached. Those fats are extracted from food with bile, which is a mixture of modified cholesterol salts that acts as a detergent to dissolve fats. The dissolved fats, in the form of chylomicrons (big fat droplets coated with a lipid layer and proteins) are produced by intestinal cells and released into the blood stream. During transit, a lipase removes the fatty acids from the triglycerides. As in all of the lipid transport systems, the protein carriers determine how the lipid contents are distributed.

If a fatty acid or triglyceride is added to a cell membrane, the lipid would get stuck in the membrane's double layer of phospholipids. Fat droplets in cells are nothing more than fats that are loaded into the membrane of a cellular vesicle until a droplet covered by a half membrane forms. The alternatives for lipid transport are the HDL and LDL (protein coated lipids of the blood), and the intracellular fatty acid-binding proteins. The proteins bound to the surface of LDLs and HDLs bind to receptors on cell surfaces and control transfer of lipids to and from cells. One example is apolipoprotein E4. This protein is intimately involved in determining risk for athersclerosis and Alzheimer’s. ApoE4 binds to its cell surface receptor via heparin. Note the blue basic amino acids that form a massive heparin-binding domain down one side of the protein.

Fatty acid-binding proteins (FABPs) are just globular proteins, with hydrophobic amino acids arranged in the center and hydrophilic, water-bonding, amino acids on the surface. I have drawn the structure of a FABP using a graphics program called Chimera to visualize X-ray crystallographic data in the National Center for Biomedical Information (NCBI) database. The continuous chain of amino acids is shown as a white ribbon and the surface of the protein is shown as a transparent overlay. The protein chain makes a cage with the hydrophobic parts of the protein pointing toward the center to make a hydrophobic-lined container for the trapped fatty acid (pink). The two ends of the protein vessel are held closed by interdigitation of tryptophans (yellow) and basic amino acids (arginine and lysine, dark and light blue). The FABP also has a nuclear translocation signal, a group of four basic amino acids and other concentrations of basic amino acids displayed linearly across the surface of the cage (not shown), that probably are involved in transport of the trapped fatty acid from the cell surface to the surface of the nuclear envelope, which is involved in phospholipid assembly.

Mice engineered to have the human ApoE4 gene develop atherosclerosis and type II diabetes. If the FABPs of the fat cells of these mutant mice have also been removed, then the mice are essentially normal. Removal of the FABPs blocks the uptake of dietary fatty acids and stimulates the production of endogenous lipids, including the omega-7 fatty acid palmitoleic acid. This fatty acid is a lipid hormone, lipokine that stimulates normal metabolism and provides protection against several inflammation-based diseases. Interestingly, palmitoleic acid accumulates abundantly in the skin of old people and is converted to nonenal that has the smell of old books.

Cao H, Gerhold K, Mayers JR, Wiest MM, Watkins SM, Hotamisligil GS. 2008. Identification of a lipokine, a lipid hormone linking adipose tissue to systemic metabolism.Cell. 134(6):933-44.