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Nutrition and Metabolism

Fat Metabolism 101

Fat, enjoy it or loathe it, is an indispensible class of building material for every single cell.  Beside the function as a component of cell membranes, fat serves the energy reserve for human as well as other animals.  Only in the last several decades, due to excess energy intake, excessive fat storage and associated overweight and obesity become an epidemic in the developed countries.  Nevertheless, we cannot live without fat.

The storage and transportation form of fat in human body, as well as dietary fat, is called triglycerides.  Each triglyceride molecule is composed of one glycerol and three fatty acids molecules.  Fatty acids are molecules with a long hydrocarbon chain attached to a carboxyl group.  The fatty acids in one triglyceride molecule or in different triglycerides molecules may be different or the same depending on the availability of the free fatty acids during triglycerides synthesis.  As the functional mode of fat, free fatty acids are components of the membrane systems in a cell, precursors for many biologically active molecules, and direct substrates for energy production via the beta oxidation pathway.

Nomenclature of fatty acids

Most natural occurring fatty acids contain even numbers of carbon atoms in straight chains.  A frequently adopted nomenclature for fatty acids is the total number of carbon atoms following the letter C and the total number of double bond following a colon.  For example, stearic acid is C18:0 (18 carbon, no double bound), arachidonic C20:4 (20 carbon, four double bonds) and docosahexaenoic acids C22:6 (22 carbon, six double bonds) etc.  

Saturated vs. unsaturated fatty acids

Fatty acids are different from each other in two structural features: the number of the carbon atoms and the number of double bond (C=C) between the carbon atoms. Fatty acids without any double bond are referred to as saturated fatty acids (SFA), with one or more double bounds are called unsaturated.  Unsaturated fatty acids are further classified to MUFAs (monounsaturated fatty acids) which have only one double bound, and PUFAs (polyunsaturated fatty acid) which have two or more double bunds.  Consumption of SFA is positively correlated with increased LDL cholesterol and higher risk of cardiovascular diseases.  Consumption of unsaturated fatty acids (regardless of MUFA or PUFA) is positively correlated with decreased LDL cholesterol and lower risk of cardiovascular diseases. 

ω−3 vs. ω−6

From the nutrition point of view, it is important to distinguish two types of PUSFs. One type is the w-3 fatty acids, which are also known as omega-3 fatty acids or n−3 fatty acids in literature. The other type is the w-6 fatty acids, also known as omega-6 or n-6 fatty acids.

The ω−3 fatty acids are PUFAs with a double bond starting after the third carbon atom from the methyl end of the carbon chain. The most common ω−3 fatty acids in nutrition literature include α-linolenic acid (ALA, C18:3), eicosapentaenoic acid (EPA, C20:5), and docosahexaenoic acid (DHA, C22:6), all of which are fund in fish oils, algal oil and many plant seeds oils.  Omega-3 fatty acids provides many benefits to human health with regard to its cardiovascular diseases prevention, anti-inflammation and possibly anti-cancer functions. 

The ω−6 fatty acids are PUSFs with a double bond starting after the sixth carbon atom from the methyl end of the carbon chain. The most common ω−6 fatty acids include linoleic acid (LA, C18:2) and arachidonic acid (AA, C20:4).  Linoleic acid is an essential fatty acid to human body although it is abundantly available from plant originated food oils (palm, soybean, rapeseed, and sunflower).  Arachidonic acid is not an essential fatty acid to human body since it can be synthesized from linoleic acid.  Meat, dairy products, eggs are the major food source for arachidonic acid. Due excess intake of ω−6 fatty acids in modern human life style, the negative impact of this type of fatty acids to human health is more noted than their important structural and regulatory functions in a normal cell. Excess intake of ω−6 fatty acids is often associated with heart attacks, thrombotic stroke, arrhythmia, arthritis, osteoporosis, inflammation, mood disorders, obesity, and cancer.  For people carrying the APOA5 SNP -1131T>G, an intake of ω−6 fatty acids exceeds 6% of the total energy becomes harmful (See the APOA5 and Triglycerides Management review).

Table 1.  Common natural fatty acids in human diet

Types Common name Structure Source
SFA Lauric C12 : 0 Coconut fat, palm kernel oil
Myristic acid C14 : 0 Mike, coconut fat
Palmitic acid C16 : 0 Palm oil, milk, butter, cheese, cocoa butter, animal meat
Stearic acid C18 : 0 Palm oil, milk, butter, cheese, cocoa butter, animal meat
MUFA Palmitoleic acid C16 : 1 Marine animal oil
Oleic acid C18 : 1 Olive oil, canola, most dietary fat
ω-6 PUFA Linoleic acid (LA) C18 : 2 Corn oil, soybean oil, sunflower seeds oil and peanut oil
Arachidonic acid (AA) C20 : 4 Small amount in animal fat
ω-3 PUFA α-Linolenic acid (ALA) C18 : 3 Flaxseeds oil
Eicosapentaenoic acid (EPA) C20 : 5 Fish oil, marine algae
Docosahexaenoic acid (DHA) C22 : 6 Fish oil, marine algae

Essential fatty acids

Essential fatty acids are the ones human body cannot synthesize, thus have to come from dietary intake.  There are two essential fatty acids for human.  On is the omega-3 fatty acid α-linolenic acid (ALA, C18:3) and the other the omega-6 fatty acid linoleic acid (LA, C18:2).  Deficiency of essential fatty acids would lead to retarded growth, dermatitis, kidney lesion and early death.

Trans vs. cis fat

In unsaturated fatty acids, the orientation of the two hydrogen atoms adjacent to a double bond has a great impact on the chemical property of the molecule.  When those two hydrogen atoms are orientated in opposite directions, they are called trans. When they are oriented in the same direction, they are cis.  Most natural unsaturated fatty acids are cis.  Trans fat is rare in natural food sources but is abundant in food industry as the result of artificial hydrogenation of natural oil.  Trans fat is easier to process in food industry but the hydrogenation destroys the essential fatty acids and renders PUFAs the property of saturated fatty acids. Therefore, they are considered health hazard and are banned in some cities in the United States.  The most abundant trans fat is found in the artificial butter margarine.

Fat as energy reservoir

In human and animals, excess calorie from diet, regardless if it is from carbohydrate or from fat, is converted to and stored as fat. But when the body requires this energy again, i. e. during fasting or starvation, the stored triglycerides are cleaved to give 3 fatty acid chains and 1 glycerol molecule in a process called lipolysis. The 3 fatty acids provide energy through a process called beta oxidation pathway.  The resulting molecules of beta oxidation pathway acetyl-CoA enters another process called the TCA cycle (tricarboxylic acid cycle, also known as Krebs cycle or the citric acid cycle) and produces even more energy.  The glycerol is converted to glucose, and gives cells energy via glycolysis pathway and TCA cycle.  Fatty acids can also been converted into ketone bodies, which refer to three molecules acetone, acetoacetic acid, and beta-hydroxybutyric acid that are produced during fatty acids breaking down for energy in the liver and kidney. They are valuable energy source since they are water-soluble and easy to be transported across the blood-brain barrier.  In the brain, ketone bodies can be readily converted to acetyl-CoA and fed into the Krebs’ cycle for energy production.  At conditions when the routine energy source glucose is limited (e.g., during fasting, strenuous exercise, low carbohydrate diet), the brain can get up to 70% energy from ketone bodies.

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