# 6.3 Functions: Lipids

Structuring cell membranes. The cell membrane constitutes a barrier for the cell and controls the flow of material in and out of the cell.
Energy storage. Triglycerides are an efficient form of energy storage that can be mobilized when fuel is needed.
Transmission of information in cells (signal transduction). Lipid hormones, like steroids and eicosanoids, also mediate communication between cells.
Cellular metabolism. The fat-soluble vitamins A, D, E, and K are required for metabolism, usually as coenzymes.

## 6.3.1 Essential fatty acids

Certain fats are defined as 'essential' because:
* The body cannot make them;
* They are required for normal cell, tissue, gland, and organ function, for health, and for life;
* They must be provided from outside the body, through food or supplements;
* They can come only from fats (hence fat-free diets cannot supply them);
* Their absence from the diet will eventually kill;
* Deficiency results in progressive deterioration, can lead to death;
* Return of essential fatty acids to a deficient diet reverses the symptoms of deficiency and results in a return to health.
Omega-6 fatty acids What are thishttp://www.dietriffic.com/2012/07/12/omega-6-fatty-acids/ ? Omega 6 is a polyunsaturated fat (or PUFA) which is essential to the body, as is omega 3. Neither of these fats are produced by the body, hence the “essential” part, so you must get them via your diet. Just to clarify, the main difference between polyunsaturated fat and monounsaturated fat (MUFA) is in the structure. Monounsaturated fatty acids (like olive oil) are linked by one double bond. Polyunsaturated fats are linked by multiple double bonds. This makes polyunsaturated fats more unstable, especially during processing. In fact, even small amounts of light, moisture, air or heat may damage polyunsaturated fats. This is one reason why it is so important to choose cooking oils carefully. Remember, “vegetable oil” does not automatically equal a healthier option.
Possibly Ineffective and Insufficient Evidence
Possibly Ineffective for: Improving mental development or growth in infants when arachidonic acid (an omega-6 fatty acid) is used in infant formula.
Insufficient Evidence for:
* Increasing good cholesterol levels (HDL).
* Lowering bad cholesterol levels (LDL).
* Reducing the risk of heart disease.
* Reducing the risk of cancer.
Omega-6 Fats Shorter-chain: The shorter-chain form of omega-6 is linoleic acid (LA), which is the most prevalent PUFA in the Western diet, is abundant in corn oil, sunflower oil, soybean oil and canola oil.
Longer-chain: The longer-chain form of omega-6 is arachidonic acid (AA), which is an important constituent of cell membranes and a material your body uses to make substances that combat infection, regulate inflammation, promote blood clotting, and allow your cells to communicate. AA is found in liver, egg yolks, animal meats and seafood.

#### Introduction

Omega-6 fatty acids are cis polyunsaturated fatty acids (Panel on Macronutrients, 2005). {Please refer to 4.1 Defining Lipids for more information regarding fatty acid structure.} There are several omega-6 fatty acids, but the only essential omega-6 fatty acid is linoleic acid (Panel on Macronutrients, 2005). {Remember that an essential nutrient is one that humans cannot synthesize and must get from their diet (Jaret, 2011).} Linoleic acid has the structural formula CH$_3$(CH$_2$)$_3$(CH$_2$CH=CH)$_2$(CH$_2$)$_7$COOH (Moore, 2011). In addition to linoleic acid, other important omega-6 fatty acids include γ-linolenic acid, dihomo-γ-linolenic acid, arachidonic acid, adrenic acid, and docosapentaenoic acid (Panel on Macronutrients, 2005).

#### Functions

As with other fatty acids, linoleic acid is primarily (98%) consumed as a component of triglycerides (Panel on Macronutrients, 2005). Like other fatty acids, linoleic acid is a major source of energy (Panel on Macronutrients, 2005), and it helps the body absorb the fat-soluble vitamins (Panel on Macronutrients, 2005). Fatty acids also play a role in cell signaling and the expression of genes related to lipid and carbohydrate metabolism (Panel on Macronutrients, 2005).
In addition to the above functions common to all fatty acids, linoleic acid has unique functions within the body. It is a component of membrane structural lipids and functions in specific cell signaling pathways (Panel on Macronutrients, 2005). Linoleic acid is required for the synthesis of other omega-6 fatty acids, which are important for normal epithelial cell function (specifically, maintaining the epidermal water barrier) (Panel on Macronutrients, 2005). Two omega-6 fatty acids, arachidonic acid and dihomo-γ-linolenic acid, are also precursors to eicosanoids (Panel on Macronutrients, 2005).
Eicosanoids are local hormones (affecting the cell that produces them and neighboring cells, but not entering the bloodstream), such as prostaglandins, thromboxanes, and leukotrienes (Moore, 2011). There are many prostaglandins with various functions, but they all lower blood pressure, induce contractions in smooth muscles, and act as part of the inflammatory response system (Moore, 2011). Thromboxanes are important in blood clotting (Moore, 2011). Leukotrienes are produced by white blood cells; they are associated with allergies (Moore, 2011).
Arachidonic acid is also important in the cell membranes of the retina and brain (Duyff & Association, 2006). It is critical for eye and brain development in infants, especially premature infants (Duyff & Association, 2006). Some infant formulas are now supplemented with arachidonic acid (in addition to linoleic acid), although the FDA has only approved these formulas for full-term infants, and the benefits of this arachidonic acid supplementation are inconclusive (Duyff & Association, 2006).

#### Food Sources and Dietary Recommendations

Omega-6 fatty acids are found mostly in plant-derived sources, such as nuts, seeds, and certain vegetable oils (corn oil, soybean oil, and sunflower oil) (Jaret, 2011). The main dietary form of omega-6 fatty acids is linoleic acid (Jaret, 2011). Conjugated linoleic acid can be found in dairy and meat products from ruminants {please refer to “Conjugated Linoleic Acid” below for more information} (Panel on Macronutrients, 2005). The AI for linoleic acid (based on the median intake in the United States for which there are no symptoms of deficiency in healthy persons) is 17g per day for young men and 12g per day for young women (Panel on Macronutrients, 2005). The American Heart Association recommends that omega-6 fatty acids provide at least 5% to 10% of food calories (Jaret, 2011).

#### Deficiency

Insufficient intake of omega-6 fatty acids causes several distinct symptoms and clinical signs: rough and scaly skin, rash, reduced growth, and an elevated ratio of eicosatrienoic acid to arachidonic acid (triene to tetraene) (Panel on Macronutrients, 2005). {Please refer to 4.4.2.1 Essential fatty acid deficiency for more information.}

#### Excess

No UL for omega-6 fatty acids has been set because there is not enough evidence to establish one (Panel on Macronutrients, 2005). Some studies have suggested that intake of omega fatty acids is associated with decreased risk of many diseases, but the ratio of omega-6 to omega-3 fatty acids is important (specifically, that the ratio should be small) (Jaret, 2011) {see “Omega-6 to Omega-3 Fatty Acid Ratio” below}. {Please refer to 4.4.1 Lipid intake: Excess for more information.}

#### Omega-6 to Omega-3 Fatty Acid Ratio

In addition to linoleic acid, there is one other essential fatty acid: alpha-linolenic acid, an omega-3 fatty acid that is the precursor to other omega-3 fatty acids in the body (Duyff & Association, 2006). The omega-3, omega-6, and omega-9 fatty acids compete within cells for the same enzyme (Δ6 and Δ5 desaturase); this enzyme’s activity is reduced by both the substrates and the products of its reaction, as well (e.g., linoleic acid, alpha-linolenic acid, arachidonic acid) (Panel on Macronutrients, 2005). Therefore, consuming too much of either linoleic acid or alpha-linolenic acid (or other omega-6 or omega-3 fatty acids) could inhibit the production of both omega-6-derived and omega-3-derived eicosanoids (Panel on Macronutrients, 2005).
The typical American consumes 15 times as many omega-6 fatty acids as omega-3 fatty acids; while throughout most of human evolution, consumption of the two types of fatty acids was approximately the same (Simopoulos, 2002). Over-consumption of omega-6 fatty acids and a very high omega-6:omega-3 ratio are associated with increased risk of cardiovascular disease, cancer, inflammatory diseases (such as asthma) and autoimmune diseases (such as rheumatoid arthritis) (Simopoulos, 2002). {Please refer to 4.3.1.2 Omega-3 Fatty Acids, 4.4 Lipid Intake, and 4.4.3 Omega-3 Fatty Acids and Health for more information regarding sources of omega-3 fatty acids and their role in health.}

#### Conjugated Linoleic Acid

Conjugated linoleic acid (CLA) refers to several different isomers of linoleic acid with adjacent double bonds (Panel on Macronutrients, 2005). There is limited evidence regarding two of the isomers’ biological activity: cis-9,trans-11 (inhibits carcinogenesis and atherogenesis) and trans-10,cis-12 (reduces adipocytes’ uptake of lipids and inhibits atherogenesis) (Panel on Macronutrients, 2005). CLA is present in dairy products and meat from ruminants due to a microorganism present in ruminants’ digestive tract (Panel on Macronutrients, 2005). Cis-9,trans-11 CLA can be converted to vaccenic acid (in a reversible process) by mammalian cells (Panel on Macronutrients, 2005). On the other hand, trans-10,cis-12 CLA can be converted reversibly into trans-10 octadecenoic acid only by a microorganism since mammalian cells lack the necessary enzyme; therefore, consumption of food containing trans-10,cis-12 ClA is the only way to get this isomer (Panel on Macronutrients, 2005).

#### References

* ↑ http://www.webmd.com/vitamins-supplements/ingredientmono-496-OMEGA-6%20FATTY%20ACIDS.aspx?activeIngredientId=496&activeIngredientName=OMEGA-6%20FATTY%20ACIDS
* ↑ http://www.fitday.com/fitness-articles/nutrition/fats/omega-6-vs-omega-3-fatty-acid-whats-the-difference.html
Duyff, R. L., & Association, A. D. (2006). American dietetic association complete food and nutrition guide. (3rd Ed. ed.). Hoboken: Wiley. Jaret, P. (2011, March 2). Understanding of the Omega Fatty Acids. Retrieved from http://www.webmd.com/diet/healthy-kitchen-11/omega-fatty-acids Moore, J. (2011). Biochemistry for dummies. (2 ed.). Indianapolis: Wiley Publishing. Panel on Macronutrients, Food and Nutrition Board (FNB), Institute of Medicine (IOM), The Panel on Macronutrients, Subcommittees on Upper Reference Levels of Nutrients and Interpretation and Uses of Dietary Reference Intakes, and the Standing Committee on the Scientific Evaluation of Dietary Reference Intakes. (2005). Dietary reference intakes for energy, carbohydrate, fiber, fat, fatty acids, cholesterol, protein, and amino acids (macronutrients) (0-309-08525-X). Retrieved from The National Academies Press website: http://books.nap.edu/openbook.php?record_id=10490 Simopoulos, A. P. (2002). The importance of the ratio of omega-6/omega-3 essential fatty acids.Biomedicine & Pharmacotherapy, 56(8), 365–379. doi: http://dx.doi.org/10.1016/S0753-3322(02)00253-6
Omega-3 fatty acids Omega-3 fatty acids are a form of polyunsaturated fat that the body derives from food. Omega-3s (and omega-6s) are known as essential fatty acids (EFAs) because they are important for good health. The body cannot make these fatty acids on its own so omega-3s must be obtained from food http://www.nlm.nih.gov/medlineplus/ency/imagepages/19302.htm .
What can high-omega-3 foods do for you?
* help prevent cancer cell growth
* reduce the risk of becoming obese and improve the body's ability to respond to insulin by stimulating the secretion of leptin, a hormone that helps regulate food intake, body weight and metabolism, and is expressed primarily by adipocytes (fat cells)
* reduce the production of messenger chemicals called cytokines, which are involved in the inflammatory response associated with atherosclerosis
* increase the activity of another chemical derived from endothelial cells (endothelium-derived nitric oxide), which causes arteries to relax and dilate
* inhibit thickening of the arteries by decreasing endothelial cells' production of a platelet-derived growth factor (the lining of the arteries is composed of endothelial cells
* decrease platelet aggregation, preventing excessive blood clotting
* lower the amount of lipids (fats such as cholesterol and triglycerides) circulating in the bloodstream
* Maintain the fluidity of your cell membranes
* Keep your blood from clotting excessively
* Reduce inflammation throughout your body
There are two major types of omega-3 fatty acids in our diets http://www.hsph.harvard.edu/nutritionsource/omega-3/ :
* One type is alpha-linolenic acid (ALA), which is found in some vegetable oils, such as soybean, rapeseed (canola), and flaxseed, and in walnuts. ALA is also found in some green vegetables, such as Brussels sprouts, kale, spinach, and salad greens.
* The other type, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), is found in fatty fish. The body partially converts ALA to EPA and DHA.
We do not know whether vegetable or fish omega-3 fatty acids are equally beneficial, although both seem to be beneficial. Unfortunately, most Americans do not get enough of either type. For good health, you should aim to get at least one rich source of omega-3 fatty acids in your diet every day. This could be through a serving of fatty fish (such as salmon), a tablespoon of canola or soybean oil in salad dressing or in cooking, or a handful of walnuts or ground flaxseed mixed into your morning oatmeal.

## 6.3.2 Triglycerides

Triglycerides are the most complex fat and the main type of fat in the body. They are the result of digesting the fat eaten from meals. Triglycerides are also made inside the body from sources of energy like protein and carbohydrates.
Triglycerides are found in the blood as a type of lipid and make up about 95 percent of all dietary fats. The calories that are consumed while eating are in the form of carbohydrates, proteins, and fats. The other calories that are not needed for immediate use are converted into this type of lipid and are stored in the body’s fat cells (Hal Bender, 2001, 2003). This leads to the point that the main function of triglycerides is to store energy for later use. The fat cells that hold the triglycerides holds these molecules until the body indicates that it is in need of energy, such as in between meals (Mayo Clinic, 1998–2015). With the help of hormones, these stored triglycerides are released in order to provide this energy between meals. However, if more calories are consumed than burned by the body, the body’s triglyceride level will increase, and this may lead to negative effects. Without triglycerides the body would run out of energy, unless calories are being constantly consumed.
Triglycerides include saturated, unsaturated, monounsaturated, polyunsaturated, and trans fats. Saturated fats have single bonds and have the maximum number of hydrogen bonds. They should be avoided, as they are the main cause of high LDL levels. Unsaturated fats lack hydrogen bonds and have at least one double bond that is considered the “point of unsaturation.” Monounsaturated fats lack two hydrogen atoms and have one double bond, while polyunsaturated fats lack at least four hydrogen atoms with two or more double bonds. Polyunsaturated fats are essential and are obtained through diet. Two common forms of polyunsaturated fats are linoleic acid (omega-6) and linolenic acid (omega-3). Trans fat are similar to saturated fats in the way they act. They are linked to heart disease and trans fats were originally created to to increase the shelf life of products protecting against oxidation, a process known as hydrogenation. Not all trans fat is bad, for example conjugated linoleic acid, which is natural and can be beneficial.
Triglyceride (triacylglycerol, TAG or triacylglyceride): Is an ester composed of a glycerol bound to three fatty acids. It is the main constituent of vegetable oil and animal fats.
Most of the fats digested by humans are triglycerides. Triglycerides are formed from a single molecule of glycerol, combined with three molecules of fatty acid. The glycerol molecule has three hydroxyl (OH-) groups. Each fatty acid has a carboxyl group (COOH-). In triglycerides, the hydroxyl groups of the glycerol join the carboxyl groups of the fatty acid to form ester bonds. Triglycerides in normal amounts are important to good health, but high amounts of triglycerides increase the risk for heart disease and stroke. High triglycerides is also one of the components of metabolic syndrome, which is a group of health problems that occur together.Your triglyceride level is measured by a blood test called a lipid profile. A lipid profile shows your triglyceride level, total cholesterol level, HDL (good) cholesterol level, and LDL (bad) cholesterol level.
A blood test can be taken in order to determine whether or not a person’s triglyceride level falls within the acceptable range. Triglycerides have an important function when it comes to determining someone’s heart health. High levels of this fat can have a negative effect by increasing the risk of heart disease.
Levels of Triglycerides Important for Health There are several ranges of triglycerides to take note of when determining if someone is at an adequate level for their health (2015). • Less than 150 milligrams per deciliter (mg/dL) or less than 1.7 millimoles per liter (mmol/L) indicate a normal level of triglycerides. • 150 to 199 mg/dL (1.8 to 2.2 mmol/L) is not a significantly high level, but does indicate a borderline high range of triglycerides. • 200 to 499 mg/dL (2.3 to 5.6 mmol/L) indicates a high level of triglycerides. • 500 mg/dL or above (5.7 mmol/L or above) indicates a very high level of triglycerides.
If the triglyceride level exceeds the acceptable normal range, the high level of this fat may harden the arteries or thicken the artery walls, also known as atherosclerosis. Extremely high levels of triglycerides, 1000 mg/dL (11.29 mmol/L) may contribute to acute pancreatitis (1998–2015). High levels of triglycerides can be signs of many health defects and problems. For example, high levels may indicate hypothyroidism, liver disease, kidney disease, a sign of poorly controlled type 2 diabetes, or even indicate that there may be a genetic condition that affects how the body is able to turn stored fat into useable energy (1998–2015).
Energy They have a very important function, in that most cells in the body use triglycerides for energy. (One notable exception is the brain cells, which do not use them for energy.) They are the most concentrated form of energy found within the body, producing more than twice the amount of energy per gram than other forms of energy, protein and carbohydrates. This is why the body can store large amounts of triglycerides.
Triglycerides’ main function is storing the energy in fat for the body to use later on. When the body consumes more calories than needed, it will store the excess calories as triglycerides. They are held by fat cells that will release the triglycerides once they receive hormonal signals that indicate the body is ready to use this energy. Without triglycerides, one would have to be constantly eating in order to avoid running out of energy.
Insulation Triglycerides in your adipose tissues protect your body from changes in temperature http://www.livestrong.com/article/245739-what-are-the-benefits-of-triglycerides/#ixzz2Oa2PXJzR . The tissues form insulation around your body and cushion the internal organs to protect them against shock or blunt trauma. Glands in the skin and mucous membranes contain triglycerides that lubricate tissues to prevent dryness and irritation.
Protection of organs Triglycerides protect organs such as the heart and kidneys from damage and heat loss.
The major storage site of triglycerides is adipose tissue, white adipose and brown adipose. Adipose tissue also insulates the body to maintain an optimal temperature and cushion the internal organs.
Protecting your heart:
Some of the immunosuppressive medications you are taking may increase your cholesterol levels and/or your blood pressure. If cholesterol levels get too high, blood vessels may become partially clogged, slowing or blocking the flow of blood. This increases the risk of heart disease and stroke. Eating foods that are high in saturated fat and cholesterol can raise your blood cholesterol to unhealthy levels. There are three main types of blood cholesterol or blood lipids: low-density lipoprotein, high-density lipoprotein, and triglycerides.
Effective ways of reducing triglyceride levels and reducing the body’s chances of developing heart disease include cutting calories if you are overweight, reducing saturated fat and trans fat intake, increasing fruit and vegetable intake, drinking alcohol in moderation as it can affect the blood triglyceride levels, and completing 30 minutes of exercise 5 days a week. The FDA recommends 10% of calorie intake to be from saturated fats and a total fat caloric intake of no more than 30%. Accumulation of triglycerides themselves may not be enough to increase the risk of heart disease unless HDL levels decrease and LDL levels increase.
kidney:
People with high blood levels of triglycerides may suffer from reduced kidney function, which can lead to kidney disease. Doctors may recommend treatments to lower triglycerides and help patients manage their kidney disease.
High cholesterol is a linked abnormality of kidney failure. People with kidney failure usually have triglyceride levels, exceeding over 200 mg because they are not broken down by the kidney, but by the enzymes in the liver. Unknown causes have made the enzymes less active during kidney failure, which causes triglycerides to accumulate.

## 6.3.3 Phospholipids

Phospholipids are a class of lipids that consist of two fatty acyl molecules esterified at the sn-1 and sn-2 positions of glycerol, and contain a head group linked by a phosphate residue at the sn-3 position.
. Phospholipids are arranged in a bilayer form and make up the plasma membrane. They are perfect for this role due to their amphipathic nature or ability to have both hydrophobic and hydrophilic regions. The hydrophobic or “water fearing” region consists of long nonpolar fatty acid tails. The tails easily interact with nonpolar molecules, but cannot interact with water. The hydrophilic or “water loving” region consists of a head that contains a negatively charged phosphate group. Since the head is polar and charged, it can interact with water. In a bilayer, the hydrophilic heads face outwards to interact with fluids and the hydrophobic tails are tucked in the interior, shielded from surrounding water. If the phospholipids have small tails, they can form a single-layered sphere (a micelle) and if they have bulky tails, they can from a hollow bilayer membrane (a liposome).
Cell membranes
All living cells and many organelles internal to cells are bounded by thin membranes. These membranes are typically described as phospholipid bilayers and are composed primarily of phospholipids and proteins.
Cell Membrane Lipids
1. Glycolipids are located on cell membrane surfaces and have a carbohydrate sugar chain attached to them. They help the cell to recognize other cells of the body.
2. Cholesterol is another lipid component of cell membranes. It helps to stiffen cell membranes and is only found in animal cells.
3. Phospholipids are a major component of cell membranes. They form a lipid bilayer, in which their hydrophilic (attracted to water) head areas spontaneously arrange to face the aqueous cytosol and the extracellular fluid, while their hydrophobic (repelled by water) tail areas face away from the cytosol and extracellular fluid. The lipid bilayer is semi-permeable, allowing only certain molecules to diffuse across the membrane.
Membrane proteins perform a variety of functions vital to the survival of organisms:
1. Cell adhesion molecules allow cells to identify each other and interact. For example, proteins involved in immune response.
2. Membrane enzymes, such as Oxidoreductases, Transferases and Hydrolases.
3. Transport proteins move molecules and ions across the membrane. They can be categorized according to the Transporter Classification database.
4. Membrane receptor proteins relay signals between the cell's internal and external environments.
Source: Alberts B, Johnson A, Lewis J, et al. Molecular Biology of the Cell. 4th edition. New York: Garland Science; 2002. The Lipid Bilayer. Available from: https://www.ncbi.nlm.nih.gov/books/NBK26871/

## 6.3.4 Sterols

Sterols, also known as steroid alcohols, are a subgroup of the steroids and an important class of organic molecules. They occur naturally in plants, animals, and fungi, with the most familiar type of animal sterol being cholesterol. Cholesterol is vital to cellular function, and a precursor to fat-soluble vitamins and steroid hormones.
Cell structure Bile Bile formation occurs by secretion of bile acids, cholesterol, phospholipids, and inorganic anions, and many transport systems for these substances have been identified in both the sinusoidal plasma membrane and canalicular membrane of hepatocytes
Bile acids (bile salts) are polar derivatives of cholesterol. They are formed in the liver from cholesterol, and drained into the hepatic duct. From there, they can enter the small intestine via the common bile duct or the gallbladder via the cystic duct. Bile is stored and concentrated in the gallbladder. As bile flows through the ducts, its consistency is modified by the addition of a bicarbonate-rich liquid. Once bile acids enter the small intestine, they aid digestion of fats and fat-soluble vitamins. The bile acids are amphipathic, with detergent properties. They emulsify fat globules into smaller micelles, increasing the surface area accessible to lipid-hydrolyzing enzymes. The bile acids also help to solubilize lipid breakdown products. Secretion of bile salts and cholesterol into the bile by the liver is the only mechanism by which cholesterol is excreted. Bonded to lipids, bile acids form micelles, which enter the blood stream. The cholesterol and bile acids of micelles are reabsorbed in the small intestine, returned to the liver via the portal vein, and may be re-secreted. This is the enterohepatic cycle.
Bile is a bitter-tasting, dark green to yellowish brown digestive fluid. In most vertebrates, bile is produced in the liver and stored in the gallbladder. Bile aids in digestion and absorption of lipids (fats) in the small intestine. Adult humans produce 400 to 800 ml of bile each day and store concentrated bile in the gallbladder (Fox, 2011). Typical mammalian bile is made up of water (82%), bile acids (12%), phospholipids (4%), cholesterol (1%) and assorted solutes (1%) (Agellon, 2002).
Bile is part of the biliary system, which helps in digestion of food, specifically emulsification of fat, and helps to excrete waste products from the liver into the duodenum and eventually exit the body through the large intestine (colon). The biliary system is made up of the liver, bile ducts, and gallbladder and other associated structures that are involved in the production and transportation of bile. Important components of bile composition include cholesterol, bile salts (also called bile acids), bilirubin (a breakdown product of red blood cells), water, body salts (like potassium and sodium), and small amounts of copper and other metals (Bowen, 2011). Other substances include fatty acids, lecithin, calcium, chlorine, and bicarbonate ions.
Bile Pathways
The liver is the largest internal and most metabolically active organ in the human body. It is responsible for producing bile for food digestion. Bile in the liver has high concentrations of water, sodium, chlorine, and bicarbonate. Bile is found throughout the biliary system and is present during digestion, especially after a high fat intake.
Bile is continually made and secreted by the liver into the bile ducts for storage in the gallbladder or for fat digestion in the small intestine. Bile is created in the liver by hepatocytes (liver cells) from cholesterol. Once food is consumed, the partially digested food, known as chyme, enters the duodenum from the stomach. Subsequently, the acid and chyme stimulate the secretion of cholecystokinin and secretin. When bile is in the gallbladder, an enzyme called cholecystokinin (CCK) senses the presence of fat in the duodenum. It then stimulates the gallbladder to contract, causing bile secretion into the duodenum through the common bile duct (Graefer, 2012). As cholecystokinin signals the release of bile, it also causes the release of digestive enzymes into the duodenum from the stomach. As a result, secretin is released and signals the pancreas and bile ducts to release bicarbonate, in an effort to neutralize the stomach acid. Once digestion is fully complete, bile acids and other enzymes return to the liver through the hepatic portal vein or move into the colon for excretion. Approximately 95% of the bile acids released into the duodenum are reabsorbed in the liver and are re-circulated 6-10 times per day (Fox, 2011). These bile acids are absorbed back into the blood within the ileum. This blood subsequently is directed to the portal vein and the sinusoids of the liver. Hepatocytes are available to separate the bile acids from the sinusoidal blood and trap them so that little escapes the liver. The bile acids are then transported from the hepatocytes to be secreted into canaliculi. This enterohepatic re-circulation process continues until the bile salts have been used efficiently.
Function
Bile acts as a surfactant to help emulsify fats in food. In most vertebrates, bile acids are amphipathic molecules in which they have both a hydrophilic and hydrophobic component. In the presence of fats in the small intestine, the hydrophobic side will migrate and attach to lipids, and the hydrophilic tail will face the outside, thus forming a micelle. These micelles allow triglycerides and phospholipids to be absorbed by the small intestine through a structure called villi and later absorbed by the lymphatic system through lacteals. In this way, bile creates an aqueous environment to ease the solubility and transport of liquids. Additionally, bile is important in the transport and absorption of fat-soluble vitamins.
Here are some basic functions of bile:
* Neutralizing and precipitating acid peptones
   * Bile is alkaline and helps neutralize any excess stomach acid before it enters the duodenum
* Stimulant for organs
* Moistening and lubrication
* Aids in absorption
* As Excrement
* Emulsification of fats
   * Bile acids, such as chenodeoxycholic and cholic acid, modify lipids to create a less hydrophobic molecule, enabling it to interact in an aqueous environment more efficiently (Agellon, 2002)
   * Emulsifiers are very important aids in metabolizing lipids (fats) as well as aiding in digestion of fat-soluble vitamins (A, D, E, and K)
* As an antiseptic
   * Bile acts as a bactericide, killing many harmful microbes that may be present in food
* Antioxidant
   * Bile helps to expel toxins from the liver when bacteria, viruses, and toxins are present
* Increases absorption of fats; integral part of the absorption of fat soluble vitamins (vitamins A, D, E, and K)
* Carries excess cholesterol out of the body by dumping it into the gastrointestinal tract where it is excreted as part of fecal matter
Bile Deficiencies and Complications
In the absence of bile, the body can’t metabolize fats, which results in deficiency of fat-soluble vitamins like Vitamins A, D, E, and K as well as utilization of calcium (Graefer, 2012). This will lead to dry skin, excessive burping after eating a meal high in fat, nausea, gas, and bloating. If bile is created in access it can be cytotoxic to the body. This can occur due to an acquired defect or physical obstruction in the body, which causes bile acid to accumulate. Common bile duct stones, narrowing of the bile duct due to inflammation, and cancer are all causes for bile accumulation (Fang, 2012). Common symptoms are jaundice (yellowing of the skin) and necrosis (damage to the mitochondria) when breakdown products of red blood cells accumulate (McEvoy, 2011). Cirrhosis – chronic liver disease where healthy liver tissue is replaced with fibrosis, scar tissues and regenerative nodules, which leads to loss of liver function. Commonly caused by hepatitis B, hepatitis C, alcoholism and fatty liver disease. Insufficient amount of bile salts – causes heartburn or chest pain, back up of toxicity, and poor hormone synthesis. Alkaline bile salts neutralize foods and emulsify fats that allow for smooth digestion. Also abdominal tightness, bloating and difficulty digesting fats occur (McEvoy, 2011). Gallstones (also referred to as cholelithiasis) – salts and cholesterol become out of balance and a build up of toxins occurs in the liver creating stones. These stones can develop from build up of cholesterol, bilirubin, calcium salts, or a mix of these.
Uses of Bile:
Bile Soap - Bile from slaughtered animals can be mixed with soap. It is found to remove tough stains from textiles if applied a few hours before washing.
Bear Bile - Ursodeosycholic acid, which is found in bear bile, has been used in China for hundreds of years for medicinal purposes. It is found to be therapeutically useful for treating primary biliary cirrhosis and dissolving gallstones (Agellon, 2002). This process of milking bears for their bile is legal in China, but with recent decreases in the bear population more individuals are speaking out against caging bears and harvesting bear bile (Bristow, 2012).
References
Agellon, L. (2002). “Metabolism and Function of Bile Acids”. Biochemistry of Lipids, Lipoproteins and Membranes, 4th, 433-448.
Bowen, R. (2001, Nov 23). Secretion of bile and the role of bile acids in digestion. Retrieved from http://biology.about.com/library/organs/bldigestliver3.htm
Bristow, M. (2012, March 1). China bear bile farms stir anger among campaigners. BBC News. Retrieved from http://www.bbc.co.uk/news/world-asia-china-17188043
Fang Y, Gurusamy KS, Wang Q, Davidson BR, Lin H, Xie X, Wang C. Pre-operative biliary drainage for obstructive jaundice. Cochrane Database of Systematic Reviews 2012, Issue 9. Art. No.: CD005444. DOI: 10.1002/14651858.CD005444.pub3.
Fox, S. (2011). Human physiology. (12 ed.). New York, New York, USA: McGraw-Hill. ISBN 978-0-07-337811-4.
Graefer, D. (2012). What is the gallbladder?. Retrieved from http://www.gallbladderattack.com/gallbladder.shtml
McEvoy, M. (2011, Sept 14). Bile deficiency: Heartburn, poor digestion, toxicity. Retrieved from http://metabolichealing.com/key-integrated-functions-of-your- body/gut/bile-deficiency-heartburn-poor-digestion-toxicity/
Staels, B., & Fonseca, V.A. (2009). Bile Acids and Metabolic Regulation: Mechanism and clinical responses to bile acid sequestration. Diabetes Care, 32 (Suppl_2).

### 4.3.4.3 Hormones

Hormones are chemical signaling molecules produced by endocrine glands and secreted directly into the bloodstream. They travel through the bloodstream to certain organs and tissues, where they bind to cell sites (receptors). When bound to receptors, hormones can trigger different responses. They allow for the communication of information throughout the body.
Example of hormones:
Cortisol:
Cortisol is a sterol hormone produced in the adrenal glands. It is released in response to stress, fasting, food, exercising and psychosocial stressors. Cortisol helps to regulate energy to meet demands placed on the body. Cortisol raises the level of glucose in the blood and helps the brain use glucose. It decreases functions that are not as important during the fight or flight response. For instance, it suppresses the digestive and reproductive systems and alters the immune system response. Cortisol also affects mood, motivation and fear.
Vitamin D:
Vitamin D is technically a hormone rather than a vitamin. It is essential for normal growth and development. It helps maintain bones and teeth and influences the metabolism of calcium and phosphorus. With the help of sunlight, the body can synthesize vitamin D from cholesterol in the skin. Vitamin D qualifies as a hormone because it is manufactured in the body, travels to parts of the body and can trigger a response.
The primary target sites for vitamin D are the intestines, kidneys and bones. These components respond to the influence of vitamin D by making calcium available for bone growth. Vitamin D is needed to make the protein that binds calcium in the intestinal cells. A deficiency of vitamin D creates a calcium deficiency too since calcium absorption is hindered without vitamin D.
Sources:
Morris HA. Vitamin D: A Hormone for All Seasons - How much is enough? Understanding the New Pressures. Clinical Biochemist Reviews. 2005;26(1):21-32.
National Center for Biotechnology Information (US). Genes and Disease [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 1998-. Glands and Hormones. Available from: https://www.ncbi.nlm.nih.gov/books/NBK22231/
* ↑ http://www.whfoods.com/genpage.php?tname=nutrient&dbid=84
* ↑ http://www.news-medical.net/health/Triglycerides-What-are-Triglycerides.aspx
* ↑ http://www.functional-fitness-facts.com/what-are-triglycerides.html
* ↑ http://cholesterol.emedtv.com/triglycerides/triglycerides.html
* ↑ http://www.vitalhealthzone.com/health/glossary/t/triglycerides.html
* ↑ http://en.wikipedia.org/wiki/Sterol
* ↑ http://www.turkgastro.org/pdf/559.pdf