Fats make membranes

Limiting autoimmune damage

Specific and broad-spectrum antibiotics can kill identified and unidentified parasites (which often make anti-inflammatory messengers) and they frequently leave immune-inciting dead bodies, parasitic biofilm and eggs behind.  

Ordinary sugar is easily procured now (especially excessive fructose) and results in metabolic pampering, spurring painful inflammatory addictive behavior creating lack of fitness, flabby muscles and storage of toxins.  Although satiating, dietary fat has become feared.  

The mechanical idea of counting calories causes dietary fats to be wrongly shunned (fat has far more calories than protein or carbohydrates).  Chronic stress (like heavy metals and/or parasitic biofilm) is structurally apoptotic and switches metabolism so that fats are made and stored.  Confusingly, intermittent similar stress instead triggers beneficial hormetic change that results in increased adaptability and fitness.  

One of Weston Price’s biggest contributions to nutrition science was fat-soluble activators, which serve as potent catalysts for mineral absorption. Without them, minerals cannot by used by your body, no matter how plentiful they may be in your diet. 

He identified three primary fat-soluble activators: vitamins A and D, and one he called “Activator X.”  Activator X was in fatty parts of animals (especially the organ meats) that fed on young green growing plants or microorganisms, as well as in oily fish and shellfish. This powerful nutrient is now thought to be vitamin K2.

Vitamin D is required for mineral metabolism, healthy bones, optimal nervous system function, muscle tone, reproductive health, insulin production, and protection from depression and every type of illness. Vitamin D’s benefits keeps growing. However, it’s important to realize that these nutrients are dependent on the animal having been raised and fed in a natural manner.

“The vital roles of these fat-soluble vitamins and the high levels found in the diets of healthy traditional peoples confirm the importance of pasture-feeding livestock. If animals are not consuming green grass, vitamins A and K will be largely missing from their fat, organ meats, butterfat and egg yolks; if they are not raised in sunlight, vitamin D will be largely missing.”

Not eating, spicy diet with fruits and vegetables and a pulsed satiating high fat diet (especially saturated fats) induces hormesis and produces a more efficient metabolism resulting in peaceful fitness; while sugars made of 5-sided rings make biofilm that is less virulent as well as promote less immune arousal and inflammation. 

Cell division is set off by light.  There is a conserved coupling between circadian clock and cell cycle.  Our immune system won't make new cells (that confine immune response and keep it silent) without some protein and adequate first light.  Instead the switch is made without enough early protein (gradually each day) to inflammatory chemistry distressing every cell.

Our number one ally is a symbiotic biofilm (and its favorite home and food is fiber (which is indigestible by us).  The digestive biofilm uses fermentation to produce gas (and one can smell a desired sulfur surfeit) while nutrifying, messaging and protecting with short-chain fatty acids.

On the other hand, our most difficult foe is a pathogenic biofilm that has become systemic (and parasites are a frequent cause).  Host antioxidant systems (which protect us from inflammation) rarely become exhausted unless one's helpful biofilm has made the switch to harmful.  

The primary weapon of our immune system is oxidation via ROS or RNS and this response is frequently surreptitiously excessively stimulated by sugars and heavy metals that at the same time also attract parasitic biofilm, which also endlessly stimulates inflammation as its favorite food.  

Our cells relatively high ability to enzymatically quench (by making acids) produced highly alkaline free radicals allows our whole-body survival.  Too much membrane "fluidity" makes the entire cell irritable and likely to trigger inflammatory damage and extremely too much mimics the chaos of a damaged cell.

Uncontrolled inflammation underlies many conditions.  Fatty acids act in many ways on different levels; they bind to cell surface and intracellular receptors that control inflammatory cell signaling and gene expression. 

The key issue in the digestion and absorption of fats is solubility: lipids are hydrophobic, and thus are poorly soluble in the aqueous environment of the digestive tract.  

The digestive enzyme, lipase, is water soluble and only works at the surface of fat globules.  Digestion is greatly aided by emulsification, the breaking up of fat globules into much smaller emulsion droplets. 

Bile salts and phospholipids are amphipathic molecules in bile.  Motility in the small intestine breaks fat globules apart into small droplets that are coated with bile salts and phospholipids, keeping larger droplets from re-forming.

The emulsion droplets are where digestion occurs.  Emulsification greatly increases the surface area where water-soluble lipase can work to digest TAG. Another factor that helps is colipase, an amphipathic protein that binds and anchors lipase at the droplet surface. 

After digestion, monoglycerides and fatty acids associate with bile salts and phopholipids to form micelles. Micelles are about 200 times smaller than emulsion droplets (4-7nm versus 1µm for emulsion droplets). 

Micelles are necessary to transport the poorly soluble monoglycerides and fatty acids to the surface of the enterocyte where they can be absorbed.  Micelles also contain fat soluble vitamins and cholesterol.  Micelles are small enough to fall between microvilli.

Micelles are constantly breaking down and re-forming, feeding a pool of monoglycerides and fatty acids in solution.  Only freely dissolved monoglycerides and fatty acids can be absorbed, not the micelles. 

Because of their nonpolar nature, monoglycerides and fatty acids can just diffuse across the plasma membrane of the enterocyte.  Some absorption may be facilitated by specific transport proteins. 

Once inside the enterocyte, monoglycerides and fatty acids are re-synthesized into triiaglycerols (TAGs), commonly called triglycerides.  The TAGs are packaged, along with cholesterol and fat soluble vitamins, into chylomicrons. Chylomicrons are lipoproteins, special particles that transport lipids in the circulation, where triglycerides help bidirectional communication. 

Chylomicrons are released by enterocyte exocytosis.  These particles are too large for capillaries. Instead they enter lacteals, lymphatics that are at the center of each villus. Chylomicrons then flow into the circulation via lymphatic vessels, which drain into the general circulation at the large veins in the chest.

Chylomicrons deliver absorbed TAG to cells.  TAG in chylomicrons and other lipoproteins is hydrolyzed by lipoprotein lipase (LPL), an enzyme on capillary endothelial cells. Monoglycerides and fatty acids released from digestion of TAG then diffuse into cells.  LPL is on endothelial cells in the heart, muscle and fat.  LPL is a homodimer, with dual functions of triglyceride hydrolase and ligand/bridging factor for lipoprotein uptake. 

Excess caloric consumption not only results from undisciplined eating, intestinal bacteria contribute to changes in appetite and metabolism.  Lacking TLR5, the wrong type of bacteria overgrow.  When overgrown bacteria were transferred to normal mice, they developed metabolic syndrome (food cravings and obesity).

In sharp contrast to the stomach and most of the small intestine, colonic contents teem with bacteria, mostly strict anaerobes.  Between these two extremes is a transitional zone, usually in the ileum, with moderate numbers of both aerobes and anaerobes.  The number and type of bacteria in the GI tract vary, partly due to pH and/or proteins and lipids that escape digestion and absorption.

Cell membranes are mostly made up of fatty acids held together by phospholipids. Phospholipids align fatty acids into bi-layers (instead of just being fat blobs) and give the cell its elasticity, fluidity and electrical potentials, enabling compounds to move in and out.  Membranes retain the electrical charges of calcium, magnesium and potassium ions. 

Cholesterol is consumed by beneficial lactic acid bacteria and bifidobacteria in the human gut.  Organic acid urine testing is non-invasive and diagnoses many metabolic individualities.

Changes in fatty acids modifies membrane fluidity, lipid raft formation and signaling leading to different gene expression and changes lipid and peptide mediators.  Inflammatory cells have more n-6s, arachidonic acids (AAs) in their phospholipids.

The types of fatty acids in cell membranes determine how they manage inflammation. Too many vegetable oils and not enough saturated fats make sensitive membranes. 

Essential fatty acids like DHA and GLA help cell membranes function better.  Cell membranes in good condition also produce hyaluronic acid to help maintain structure.

The cell membrane is very sophisticated and is a constantly changing fluid mosaic.  Hundreds of thousands of saturated fat 'rafts' prop up and position various glycoprotein receptors to punctuate this very changeable and intricate bilayer of phospholipids, and some even display antennae.  

This changeable, intelligent, communicative and complicated outer membrane is connected by structural cytoplasmic membranes (that can also remember, manufacture and transport) to organelles, that are surrounded by membrane and membrane also surround the nuclear membrane with its pores. 

Serotonin signals satisfaction and is triggered by insulin.  Insulin increases the tryptophan ratio over the other amino acids. Insulin rises almost immediately, the pancreas releases stored insulin. Insulin then produces energy and moves glucose from blood to cells. 

Insulin organizes fuel for storage or oxidation.  Insulin has big effects on carbohydrates and lipids, and large influences on proteins and minerals.  Insulin increases cell permeability to monosaccharides, amino acids and fatty acids while it accelerates glycolysis, the pentose phosphate cycle and glycogen synthesis. 

Involved in ketone-body metabolism are the anabolic hormones (insulin and growth hormone) as well as the mostly catabolic ones (glucagon, cortisol and catecholamines) .  

Ketoacidosis (ketone breath) does not always mean diabetes. It also results from a ketogenic diet (which stabilizes membranes and induces hormesis if done intermittently), processing a lot of alcohol and/or starvation (without diabetes, glucose is usually normal or low).

These hormones mostly regulate ketone-bodies at three sites: fat tissue, and its fatty acid supply to the liver; re-esterification and fatty acid oxidation in the liver; and the rate of use in the periphery.  Ketone bodies promote insulin secretion from isolated rat pancreatic islets with 5 mM-glucose, but are ineffective in its absence.

In someone without diabetes, a rise in blood amino acids (from protein metabolism) stimulates secretion of both glucagon and insulin, so blood sugar remains stable. But in those with diabetes, glucagon without insulin (or with impaired insulin response) can cause blood sugar to rise precipitously several hours after a meal high in protein.

Insulin stimulates protein synthesis--the uptake of amino acids into muscle cells (which allows more tryptophan to be a precursor to serotonin)--making proteins less available for conversion into glucose.  Glucagon stimulates the uptake of amino acids into the cells for gluconeogenesis.

Insulin lowers blood sugar, while glucagon raises it.  In the non-diabetic, these two opposing hormones ensure that the amino acids are used for protein synthesis (because of the extra insulin) but the blood sugar doesn't drop dangerously low, even if the meal is low in carbohydrate. 

As a result, blood glucose remains reasonably stable during protein metabolism.  The insulin and glucagon balance each other on blood glucose, while insulin promotes protein synthesis.

The body can use wide amounts of carbohydrates, fats and protein to make energy.  Serotonin can also stimulate insulin release.  Serotonin has a big influence on appetite, sleep, mood and learning capability.

The serotonin transporter (SERT) is a protein in the membrane that enables serotonin to be transported into the cell and it is in blood (with 60,000 miles of endothelium).  Serotonin is a measure of emotional satiety.  A blood test can predict the activity of this major satisfaction or depression network. 

Ghrelin is called the "hunger hormone" because it makes one ravenous.  Ghrelin acts on "pleasure centers," driving the desire for another cheesecake because you remember how good the first one tasted and made you feel.  Ghrelin levels are very complex.  Expectations result in big declines in ghrelin even without an indulgent meal.

Genetic polymorphisms moderate emotional behavior and changes in satisfaction and are consistent with the short allele of the SERT polymorphism being a susceptibility factor that amplifies sensitivity to both negative and positive emotional influences. 

All three high fatty acid diets influenced serotonin receptor binding, however the biggest effects occurred compared with low fat, 

i) 5-HT(2A) receptor binding was increased in the caudate putamen, but reduced in the mammillary nucleus in high saturated fat and high omega-6 diet groups; 

ii) 5-HT(2C) receptor binding was reduced in the mamillary nucleus of saturated fat group and reduced in prefrontal cortex of the omega-6 and omega-3 groups; 

iii) 5-HTT binding was reduced in the hippocampus in the omega-6 group. Overall, the omega-6s exert the most influence on serotonin receptor and transporter binding. 

After consumption of a carbohydrate-rich meal, insulin is secreted. Insulin lowers most amino acids (building blocks), except for tryptophan (a precursor to serotonin). 

Amino acids compete for transportation across the blood-brain barrier, and when there is more tryptophan, it enters the brain at a higher rate, boosting serotonin. Tryptophan is also present in many protein-rich foods, which surprisingly reduce serotonin production.

The membrane actively fine-tunes itself as conditions change.  The number and location of carbon-carbon double bonds in the phospholipid tails of the lipid bilayers, are somehow modified in real-time. 

A topologically closed membrane surrounds all cells. This membrane is not a simple semi-permeable lipid bilayer enclosing cell innards.  Even in the simplest cells, the membrane is a biological device of a staggering complexity that senses and carries many messages, mediating energy-dependent (and tightly regulated) import and export. 

Each membrane is made up of millions of phospholipids. Each phospholipid has one head and two tails. One tail is straight, and the other is wavy. Cholesterol is wedged in between in between these two tails. Another part of the membrane is the glycolipid. Glycolipids are tiny sugar molecules that protect, insulate, and exchange nutrients within the cell membrane. 

The number one part of every membrane is the phospholipid. This molecule has a head and two tails.  The phospholipid head has two hydrocarbon tails.  The head and tails of the phospholipid act like a magnet. The head has a positive charge, and tail has a negative charge. These magnet-like electric charges attract and repel, which allows nutrients to go into the cell, and waste to exit out of the cell’s membrane. The straight tail of the phospholipid is a straight chain fatty acid (a saturated fat). The crooked tail is an unsaturated fat, because of a cis double bond.   The saturated (straight) tail is rigid and solid, and seldom moves. However, the crooked tail (unsaturated) tail vibrates, it moves particles in and out of the membrane.  Most importantly, it takes a balance of both saturated, and unsaturated fats to compose, and properly maintain, the structure of phospholipids, which are the main part of cell membranes.  All membranes need cholesterol, though the amount varies with the type.  Cholesterol gives the membrane structure. Basically, the cholesterol is in between the tails of the phospholipid, and it has the same orientation as the phospholipids.  Glycoplipids are also part of cell membranes. Glycoplipids are simple sugars added to ceramides  Ceremides are a fatty acid bonded to the amino alcohol sphingosine  Synthesis of glycolipids occurs with the help of enzymes that sequentially add sugars. When the lipids need to be broken down, enzymes in the lysosome of the cell help to remove the sugar subunits.  Glycolipids protect, insulate, and help in the exchange of nutrients within the cell membrane and its “outside world.”  Glycoplipids help modulate immunity.  Glycoplipids include mannose, oligosaccarides, and arabinogalactan. In microorganisms, certain glycolipids even help survival by "tricking" our immune system into thinking they are not foreign. This helps them to evade immune surveillance. On the other hand, some viruses, bacteria (eg., cholera) also use glycolipids on their cell surface. The immune system uses these as binding sites to destroy and clear pathogens. Glycerols are part of the phospholipid structure of cell membranes, a building block. Akylglycerols have a unique bond between the two glycerols (ether bond - an oxygen bond instead of a common hydrogen bond).  The ether bond repels water, causing much attraction to fatty structures like cell membranes.  Alkylglycerols are rapidly taken up by cell membranes and are metabolized to help produce phospholipids.  Alkylglycerol promotes white blood cell production. Alkylglycerols are in bone marrow, liver and spleen as well as breast milk, and are a membrane nutrient.  As a supplement they come from shark liver oil.  An alkylglycerol is an alcohol sugar compound, two glycerols linked by an oxygen.  The alcohol part is a solvent, making glycerol fat soluble.  Most is in bone marrow (0.2%) and spleen (.05%).  Alkylglycerols are in breast milk (0.1%).  The liver makes them and membranes accumulate small amounts.  Bone marrow is the birthplace of immune cells, red blood cells and platelets.  Alkylglycerols from shark liver oil boost all three (and immunoglobulins). Traditional uses of alkylglycerols centered on wound healing, respiratory tract ailments, digestive problems, swelling in the lymphatic system (like swollen lymph nodes) and it was used for frailty (general rejuvenation).  The alkyl glycerol ether rac-1-O-dodecylglycerol inhibits the growth of two genera of yeasts, Candida and Cryptococcus. Alkylglycerols are a unique fatty nutrient with many functions.  They were first understood in a context of immune support and are moving into a broader context of basic cell nourishment.  They easily become part of cell membranes and participate in cell signaling and have diverse functions.  Alkylglycerols increase [Ca2+]i influx in human Jurkat T-cells, possibly by modulating the permeability of calcium channels. Anti-oxidants stabilize fats.  They prevent fats from going rancid, which is very dangerous.

Bacteria put in an inhospitable environment, change.  Given only incompatible food, by sensing the structure, micro-organisms adapt their digestion to accommodate to what is available.  

Some genes engineer the design of other genes.  Differences in us don't come just from differences in our genes, but also how genes are regulated.  The nucleus can genetically choose a pathway to adapt to the environment from membrane sensed conditions. 

All living cells use a similar irreducibly complex suite of DNA and RNA, enzymes and organelles to act.  DNA benefits from protection provided by the cell membrane.

Cells regulate genetic activity by controlling when and how a gene binds to its promoter.  Cells have many regulatory ways, from managing which proteins enter the nucleus to changing their structure (to control or destroy proteins).

Epigenetic methylation marks on the DNA of plants can alter the phenotype in heritable ways that remain stable up to at least eight generations.  Epigenetic methylation of steroid receptor genes in developing humans occurs with a perceived stressful childhood.  

Different paradigms resulting from different perspectves call this observed biologic change: development, adaptation, hormesis, genetics, epigenetics, evolution and/or intelligent design (creation).

The cell membrane functions like a brain, a kind of nervous system.  A cell surface can see, hear, feel and interpret messages.  The cell membrane has a form of intelligence and the ability to make decisions about how it and the entire cell will function.

Intelligence is relative, fractal and emergent.  Intelligent ecologies contain intelligent populations, which are made up of intelligent cooperative organisms, which contain intelligent cooperative prokaryotic and eukaryotic cells, which contain intelligent cooperative compartments, and those are contained by intelligent membranes.

Bringing consciousness into the body awakens.  Every cell responds and rejoices. The body loves attention.  When we meditate, rewarding chemicals are secreted which awaken inherent health potency.  Inducing parasympathetic dominance allows hormetic response.  Cells (atoms, photons or people) change behavior when observed.

Each of our approximately 75 trillion cells has infinite wisdom reflected in its outer membrane.  Together the goal is the well-being of the entire system (which also supports a symbiotic intelligent ecosystem) and both exist within a larger beneficent intelligent ecosystem. 

Cells communicate and move together as a community as they are in motion, pulsing in a rhythmical expansion and contraction arising from emptiness, spaciousness. This emptiness is full of potential.

Cells receive much information from chemicals that find receptors.  Once a message binds, other substances are created that travel.  DNA genes lying inside the nucleus are given directions by RNA to synthesize proteins.  These proteins then control and regulate the cells to coordinate with the rest of the body.

The cells are controlled by their interaction with the internal physical environment, which is also affected by one's basic attitude and especially emotions (only partly genetic).

Eicosanoids made from AA spur on inflammation.  Oral EPA and DHA increases the EPA and DHA in the membranes of cells, along with a decrease in inflammation and AA. 

EPA makes eicosanoids that are often less potent than those from AA.  EPA gives rise to E-series resolvins and DHA makes D-series resolvins and protectins.  Resolvins and protectins are anti-inflammatory.  Inflammatory cells exposed to different types of fatty acids have their function altered. 

The fatty acyl composition of phospholipids determines fluidity and function of membrane proteins.  In response to changes in cellular lipid metabolism, nuclear receptors dynamically modulate membrane composition.  

Ligand activation of liver X receptors (LXRs) drives the incorporation of polyunsaturated fatty acids into phospholipids via inducing the remodeling enzyme Lpcat3. Promotion of Lpcat3 activity ameliorates endoplasmic reticulum (ER) stress induced by saturated free fatty acids by hepatic lipid accumulation. 

Lpcat3 lack in liver exacerbates ER stress and inflammation.  Lpcat3 modulates inflammation both by regulating inflammatory kinase activation via changes in membrane composition and by affecting substrates for inflammatory mediators. This preserves membrane homeostasis during lipid stress. LXR effects metabolism through Lpcat3.

NSAIDs act as anti-inflammatories.  NSAID pro-apoptotic effect partly relies on inhibiting epidermal growth factor receptor (EGFR) signaling via less cell membrane fluidity.  NSAIDs induce a change in ratios of saturated, monounsaturated and polyunsaturated fatty acids in cell phospholipids and significantly increase cholesterol in the membrane.  

The membrane becomes composed of low electric potential phospholipids whose lateral diffusion is prohibited and the membrane stays mostly in relative gel phase.  Less fluidity blocks EGFR kinase activity and its targets, the p44-42 mitogen-activated protein kinase (MAPK) and AKT cascades (inhibition induces apoptosis in cancer cell lines).

Necrosis releases enzymes stored by lysosomes, which can digest cell components or the entire cell.  The release of intracellular content after membrane damage causes inflammation.

In contrast with apoptosis, cleanup of necrotic cell debris is generally more difficult, as the disorderly death does not send cell signals which tell nearby phagocytes to engulf.  Lack of signaling makes it harder to locate and recycle cells which die of necrosis (than if cell organelles undergo the membrane packaging of apoptosis).

Breath holding with mental calmness (especially swimming distances under water) epigenetically boosts one's buffering REDOX capacity.  Having adequate protein and balanced selenium, zinc and iodine boosts both immune efficiency and glutathione and other protectants.