OVERVIEW
• Fats or lipids are made up of cholesterol and triglycerides which cannot dissolve in aqueous plasma and need to be transported in blood by
lipoproteins.

• Lipoprotein is composed of esterified and unesterified cholesterol, triglycerides, phospholipids and apolipoproteins. The apolipoproteins act as
cofactors for enzymes involved in fat metabolism

• The major forms of lipoproteins include the following
Chylomicrons (large particles that transport dietary fat in the blood)
Very low density lipoprotein (transport endogenous triglyceride and some cholesterol)
Intermediate density lipoprotein (transport cholesterol esters and triglycerides)
Low density lipoprotein (transport cholesterol esters)
High density lipoprotein (transport cholesterol esters)

• Cholesterol metabolism has two major pathways namely the exogenous and endogenous pathways. Exogenous
pathway involves transport and metabolism of dietary lipids. Endogenous pathway involves transport and metabolism of endogenously formed
lipids

• In exogenous pathway, cholesterol and fatty acids from the diet are absorbed in the intestine. In the
intestinal cells, cholesterol becomes esterified to be transported more easily and triglycerides are formed from fatty acids and glycerol. The
cholesterol and triglycerides are incorporated into chylomicrons and transported in blood to peripheral tissues for utilisation or storage in adipose
tissue as appropriate. The remnant particles of the exogenous pathway are used to produce high density lipoprotein (HDL)

• In the endogenous pathway, triglycerides and cholesterol esters are processed to form very low density lipoprotein (VLDL) in the liver. The
VLDL is processed further to form IDL or VLDL remnants. The VLDL remnants are cleared from the circulation or become incorporated into low
density lipoprotein (LDL) which are chiefly composed of a core of cholesterol esters and a lesser amount of triglyceride. The LDL is taken up
by liver and other tissues. In the liver, LDL is converted to bile acids and excreted into the intestines. In other tissues, LDL is used to
synthesise hormones, cell membrane or stored for future use. Importantly, LDL is also taken up by macrophages and other cells which
contribute to plaque formation and atherosclerosis in blood vessels with significant consequences

CLINICAL IMPORTANCE OF CHOLESTEROL METABOLISM
• Serum lipids include cholesterol (including LDL, HDL and VLDL cholesterols) and triglycerides.

• Disorders in lipid metabolism are known as dyslipidemias resulting usually in an increase in level of serum LDL cholesterol, triglycerides,
and VLDL which are associated with serious health consequences

• Lipid levels may be abnormal due to effects of aging, consuming certain drugs (diuretics), various disorders such as diabetes, hypothyroidism
as well as inherited ones such as familial hypercholesterolemia), or lifestyle (such as following a diet high in saturated fat, leading a
sedentary and inactive life, or being overweight)

• Of the cholesterol types, LDL cholesterol is also known as bad cholesterol and is associated with an increased risk of heart disease while
HDL cholesterol is referred to as good cholesterol and reduces risk of heart disease. High levels of triglycerides are associated with
increased risk of pancreatitis

• When LDL cholesterol levels increase, they get deposited in the walls of blood vessels, resulting in plaque formation and atherosclerosis. The
atherosclerotic plaque causes narrowing of blood vessels and if blood vessels supplying heart or brain are affected, it can cause heart attack and
stroke respectively

MEASUREMENT OF SERUM LIPID PROFILE AND RECOMMENDED LEVELS
The American Heart Association recommends that all adults over 20 years should have their cholesterol checked every 4 to 6 years. Men are generally at increased risk for higher cholesterol compared to women. However, a woman’s risk increases at menopause. In persons with high cholesterol, more frequent testing is advised.

The fasting lipid profile, including total cholesterol (LDL cholesterol, VLDL and HDL cholesterol) and triglycerides is measured following a 12 hour fast. The recommended levels are given below

As per current guidelines all children between 9 to 12 years, and once again between 17 and 21 years should have serum cholesterol level checked. If there are additional risk factors such as diabetes or a family history of high cholesterol, it should be checked between 2 to 8 years and again between ages 12 and 16.

TREATMENT OF HIGH SERUM FATS
A combination of medications and lifestyle changes is usually recommended to treat high cholesterol and triglycerides.

MEDICATIONS
Cholesterol lowering drugs include statins, agents that reduce dietary absorption of cholesterol, bile acid sequestrants (which trap bile resins containing cholesterol, and prevent their reabsorption in the small intestine) and fibrates (reduce triglyceride levels of blood)

DIET SUPPLEMENTS
Omega-3 fatty acid containing supplements are readily available over the counter and used to lower triglycerides and LDL levels. They occur naturally in fish such as salmon, and nuts. Niacin is another supplement prescribed to increase HDL formation in the body

LIFESTYLE CHANGES TO REDUCE CHOLESTEROL LEVELS
• Exercise daily for at least 30 minutes of aerobic exercises. This increases HDL cholesterol levels
• Include more fiber, fresh fruits and vegetables and whole grain foods
• Consume healthy fats found naturally in foods such as nuts, avocado and olive oil
• Reduce high saturated fat foods such as red meat, cheese, full cream milk
• Quit smoking