Mono- and Polyunsaturated Fats

Monounsaturated fats are ok but not as good as the polys. Polyunsaturated fatty acids (PUFA) contain more than one double bond. Some PUFAs appear strongly beneficial in heart disease and perhaps other conditions (ref). The more unsaturated fats in your cells, the more pliable and dynamic their membranes are.

 

omega-3 fatty acids suppress cardiac arrhythmias, lower serum TAG, reduce thrombosis, and substantially reduce the risk of cardiovascular mortality. However, they do not appear to lower LDL or increase HDL in people.

• α-linolenic acid (ALA) is found in plants such as flax, soybean, and others
• docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are found in fish oils
• omega-3 derived eicosanoids are less active and antiaggregatory

omega-6 fatty acids

• linoleic acid
• gamma-linolenic acid
• arachidonic acid and eicosanoids

Saturated Fats

Saturated fats primarily come from animal sources and can have troubling health effects. They have two hydrogen atoms for each carbon in their tails, allowing them to pack closely together and leading to their solidity at room temperature.

Trans Fats

Trans fats are unsaturated fats which have been chemically modified to give them a longer shelf life, improve their taste and consistency, and increase their stability while cooking. However, this modification has serious health risks, with almost 30% of heart disease in the developed world appearing to be caused by trans fats (Mozaffarian et al, NEJM 2006). This showed:

• "a 2% increase in energy intake from trans fatty acids was associated wirh a 23% increase in the incidence of coronary artery disease"
• perhaps 20% of CHD events in the US are preventable by avoiding trans fats and replacing with omega-3 fatty acids.

 

Proposed Mechanisms of Action

act on hepatocyte, endothelial cells, adipocytes, and macrophages.

 

beware that less than 0.5 g can be called 0 grams - avoid hydrogenated fats

Cholesterol

Cholesterol, a steroid alcohol, performs a number of important functions in the body:

• a structural component of the cell membrane
• precursor of bile salts
• framework for steroid hormones, and vitamin D

As such, the cell needs a constant supply of cholesterol. Cholesterol biosynthesis and regulation is primarily mediated by the liver. From 0.2-0.5 g of cholesterol is ingested daily, and 0.8-1.0 g/day is synthesized.

Cholesterol is transported to cells on LDL particles, which contain Apo B-100 that bind to LDL receptors. Cholesterol is then used, or esterified and stored by activity of the enzyme ACAT.

The transport of cholesterol according to need is not precise, and over time there is a gradual deposition of cholesterol in the tissues, particularly the endothelium.

 

It can also be a troublesome molecule. In situations of dyslipidemia, cholesterol can accumulate on blood vessel walls and contribute to atherosclerosis. HDL and LDL are transport carriers for cholesterol in the blood.

 

 

 

Structure of Cholesterol

Cholesterol is very hydrophobic due to its four fused rings and its 8-carbon branched hydrocarbon chain. Steroids that have an 8-10 Carbon chain and a hydroxyl group are called sterols.

Most plasma cholesterol is esterified, with a FA attached to the C-3 hydroxyl group. Cholesterol esters are not normally found in membranes, and because of their hydrophobicity they must be transported either in lipoproteins or in bile salts.

 

Plant sterols are poorly absorbed and are actively transported back to the intestine. They appear to bring with them cholesterol molecules, leading to the use of plant sterol esters (ie margarine) to reduce cholesterol levels.

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Cholesterol Synthesis

Cholesterol is made in almost every tissue, though the liver, intestine, adrenal cortex and reproductive organs make the largest amounts. All the carbon atoms are provided by acetate, and NADPH is the reducing agent. It is driven by hydrolysis of the thioester bond of acetyl CoA and ATP, and occurs in the cytoplasm. Enzymes are both in the cytoplasm and on the ER membrane.

 

Three acetyl CoA molecules combine to form HMG CoA, with 6 carbons. Next, HMG-Coa is reduced to mevalonic acid by HMG CoA reductase, the rate-limiting step of cholesterol synthesis. This reaction releases CoA, making the reaction irreversible. From there many steps occur to lead to cholesterol synthesis.

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Regulation of Plasma Cholesterol

HMG CoA Reductase is regulated at the transcriptional level, by phosphorylation (inactivates), or by degradation.

• Cholesterol levels affect HMG CoA reductase mRNA and protein stability
• transcription of its gene is increased by Sterol Regulatory Element-Binding Protein (SREBP is usually associated with the ER membrane.
• Insulin upregulates HMG CoA reductase transcription, while glucagon has the opposite effect.
• Statins are structural analogues of HMG CoA, and are reversible competitive inhibitors of HPG CoA Reductase.

 

There are a number of ways to decrease plasma colesterol levels.

Dietary cholesterol has minimal effect on plasma cholesterol levels. N-6 PUFAs can reduce LDL levels, as does the Mediterranean diet, rich in monounsaturated fat. N-3 PUFAs appear not to have an effect.

Maximally decreasing dietary cholesterol and saturated fats can reduce plasma levels by up to 20%.

 

• dietary intervention - decrease cholesterol and SFAs, increase PUFAs, and add fibre
• statins - HMC CoA- reductase inhibitors
• ezetimibe - inhibits cholesterol uptake in the gut, reducing serum cholesterol by up to 20%
• vytorin - combination ezetimibe and simvastatin

 

 

 

Cholesterol Degradation

As the ring structure of cholesterol cannot be broken down, it is converted into bile acids and salts, or excreted in the bile. Some of the cholesterol is modified by fecal bacteria to form coprostanol and cholestanol.