28.9 : Cholesterol: Significance and Regulation

Although not a source of energy, cholesterol plays a significant role as a foundational structure for bile salts, steroid hormones, and vitamin D, as well as being a crucial component of plasma membranes. Approximately 15% of blood cholesterol is derived from our diet, with the remainder synthesized from acetyl CoA by the liver and intestines. Cholesterol is eliminated from the body through its conversion into bile salts, which are eventually discarded in the feces.

Considering cholesterol and triglycerides are water-insoluble, their transportation in the blood is facilitated by lipid-protein complexes known as lipoproteins. These lipoproteins help solubilize hydrophobic lipids and act as carriers to regulate lipid delivery to specific target cells.

Lipoproteins can be classified into very low-density lipoproteins (VLDLs), low-density lipoproteins (LDLs), and high-density lipoproteins (HDLs) based on their relative fat-protein composition.

The primary role of HDLs, which are abundant in phospholipids and proteins, is to collect and transport excess cholesterol from peripheral tissues to the liver, where it is degraded and forms part of the bile. These HDL particles, in their incomplete state, are released into the bloodstream by the liver, where they gradually collect cholesterol from tissue cells and artery walls. They also supply cholesterol to steroid-producing organs such as the ovaries and adrenal glands.

For adults, it's recommended to maintain blood cholesterol levels under 200 mg/dl. However, it is more important to monitor LDL and HDL levels individually, as total cholesterol alone is not always the best indicator of cardiovascular risk. Elevated LDL levels are a stronger predictor of atherosclerosis, which can lead to heart attacks and strokes, while high HDL levels are beneficial as they facilitate cholesterol removal and degradation

Beyond diet, several factors influence blood cholesterol levels. Cigarette smoking and stress lower HDL levels, while regular aerobic exercise and estrogen can decrease LDL levels and increase HDL levels. Body shape also correlates with cholesterol and fat distribution, providing insights into cardiovascular risk. Individuals with upper body and abdominal fat ("apples") tend to have higher levels of cholesterol and LDLs compared to those with fat concentrated in the hips and thighs ("pears"). This is because visceral (abdominal) fat is more metabolically active and associated with higher risks of cardiovascular diseases and metabolic syndrome.