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Blood lipids (or blood fats) are lipids in the blood, either free or bound to other molecules. They are mostly transported in a phospholipid capsule, and the type of protein embedded in this outer shell determines the fate of the particle and its influence on metabolism. Examples of these lipids include cholesterol and triglycerides. The concentration of blood lipids depends on intake and excretion from the intestine, and uptake and secretion from cells. Hyperlipidemia is the presence of elevated or abnormal levels of lipids and/or lipoproteins in the blood, and is a major risk factor for cardiovascular disease.
Short- and medium chain fatty acids are absorbed directly into the blood via intestine capillaries and travel through the portal vein. Long-chain fatty acids, on the other hand, are too large to be directly released into the tiny intestine capillaries. Instead they are coated with a membrane composed of phospholipids and proteins, forming a large transporter particle called chylomicron. The chylomicron enters a lymphatic capillary, then it is transported into the bloodstream at the left subclavian vein (having bypassed the liver).
In any case, the concentration of blood fatty acids increase temporarily after a meal.
After a meal, when the blood concentration of fatty acids rises, there is an increase in uptake of fatty acids in different cells of the body, mainly liver cells, adipocytes and muscle cells. This uptake is stimulated by insulin from the pancreas. As a result, the blood concentration of fatty acid stabilizes again after a meal.
After a meal, some of the fatty acids taken up by the liver is converted into very low density lipoproteins (VLDL) and again secreted into the blood. [1]
In addition, when a long time has passed since the last meal, the concentration of fatty acids in the blood decreases, which triggers adipocytes to release stored fatty acids into the blood as free fatty acids, in order to supply e.g. muscle cells with energy.
In any case, also the fatty acids secreted from cells are anew taken up by other cells in the body, until entering fatty acid metabolism [ clarification needed ].
The fate of cholesterol in the blood is highly determined by its constitution of lipoproteins, where some types favour transport towards body tissues and others towards the liver for excretion into the intestines.
The 1987 report of National Cholesterol Education Program, Adult Treatment Panels suggest the total blood cholesterol level should be: <200 mg/dl normal blood cholesterol, 200–239 mg/dl borderline-high, >240 mg/dl high cholesterol. [2]
The average amount of blood cholesterol varies with age, typically rising gradually until one is about 60 years old. There appear to be seasonal variations in cholesterol levels in humans, more, on average, in winter. [3] These seasonal variations seem to be inversely linked to vitamin C intake. [4] [5]
In lipid digestion, cholesterol is packed into chylomicrons in the small intestine, which are delivered to the portal vein and lymph. The chylomicrons are ultimately taken up by liver hepatocytes via interaction between apolipoprotein E and the LDL receptor or lipoprotein receptor-related proteins.
Cholesterol is minimally soluble in water; it cannot dissolve and travel in the water-based bloodstream. Instead, it is transported in the bloodstream by lipoproteins that are water-soluble and carry cholesterol and triglycerides internally. The apolipoproteins forming the surface of the given lipoprotein particle determine from what cells cholesterol will be removed and to where it will be supplied.
The largest lipoproteins, which primarily transport fats from the intestinal mucosa to the liver, are called chylomicrons. They carry mostly fats in the form of triglycerides. In the liver, chylomicron particles release triglycerides and some cholesterol. The liver converts unburned food metabolites into very low density lipoproteins (VLDL) and secretes them into plasma where they are converted to intermediate-density lipoproteins(IDL), which thereafter are converted to low-density lipoprotein (LDL) particles and non-esterified fatty acids, which can affect other body cells. In healthy individuals, most of the LDL particles are large and buoyant (less dense, also known as lb-LDL) and they are cardiovascularly neutral: they have no negative and no positive effect on cardiovascular health. In contrast, large numbers of small and dense LDL (sd-LDL) particles are strongly associated with the presence of atheromatous disease within the arteries. For this reason, total LDL is referred to as "bad cholesterol," although only a fraction of it is actually bad.
Standard chemistry panels typically include total triglyceride, LDL and HDL levels in the blood. Measuring the concentration of sd-LDL is expensive. However, since it is produced from VLDL, it can be inferred indirectly by estimating VLDL levels in the blood. That estimate is typically obtained by measuring triglyceride levels after at least eight hours of fasting, when chylomicrons have been totally removed from the blood by the liver. In the absence of chylomicrons, triglyceride levels have a much larger correlation with risk of cardiovascular diseases than total LDL levels.
After being transported to the liver by HDL, cholesterol is delivered to the intestines via bile production. However, 92-97% is reabsorbed in the intestines and recycled via enterohepatic circulation.
Cholesterol circulates in the blood in low-density lipoproteins and these are taken into the cell by LDL receptor-mediated endocytosis in clathrin-coated pits, and then hydrolysed in lysosomes.
In response to low blood cholesterol, different cells of the body, mainly in the liver and intestines, start to synthesize cholesterol from acetyl-CoA by the enzyme HMG-CoA reductase. This is then released into the blood.
Hyperlipidemia is the presence of elevated or abnormal levels of lipids and/or lipoproteins in the blood.
Lipid and lipoprotein abnormalities are extremely common in the general population, and are regarded as a highly modifiable risk factor for cardiovascular disease. In addition, some forms may predispose to acute pancreatitis. One of the most clinically relevant lipid substances is cholesterol, especially on atherosclerosis and cardiovascular disease. The presence of high levels of cholesterol in the blood is called hypercholesterolemia. [6]
Hyperlipoproteinemia is elevated levels of lipoproteins.
Hypercholesterolemia is the presence of high levels of cholesterol in the blood. [6] It is not a disease but a metabolic derangement that can be secondary to many diseases and can contribute to many forms of disease, most notably cardiovascular disease. Familial hypercholesterolemia is a rare genetic disorder that can occur in families, where sufferers cannot properly metabolise cholesterol.
Abnormally low levels of cholesterol are called hypocholesterolemia .
Cholesterol is the principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils.
High-density lipoprotein (HDL) is one of the five major groups of lipoproteins. Lipoproteins are complex particles composed of multiple proteins which transport all fat molecules (lipids) around the body within the water outside cells. They are typically composed of 80–100 proteins per particle. HDL particles enlarge while circulating in the blood, aggregating more fat molecules and transporting up to hundreds of fat molecules per particle.
Low-density lipoprotein (LDL) is one of the five major groups of lipoprotein that transport all fat molecules around the body in extracellular water. These groups, from least dense to most dense, are chylomicrons, very low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), low-density lipoprotein (LDL) and high-density lipoprotein (HDL). LDL delivers fat molecules to cells. LDL is involved in atherosclerosis, a process in which it is oxidized within the walls of arteries.
A lipoprotein is a biochemical assembly whose primary function is to transport hydrophobic lipid molecules in water, as in blood plasma or other extracellular fluids. They consist of a triglyceride and cholesterol center, surrounded by a phospholipid outer shell, with the hydrophilic portions oriented outward toward the surrounding water and lipophilic portions oriented inward toward the lipid center. A special kind of protein, called apolipoprotein, is embedded in the outer shell, both stabilising the complex and giving it a functional identity that determines its role.
Very-low-density lipoprotein (VLDL), density relative to extracellular water, is a type of lipoprotein made by the liver. VLDL is one of the five major groups of lipoproteins that enable fats and cholesterol to move within the water-based solution of the bloodstream. VLDL is assembled in the liver from triglycerides, cholesterol, and apolipoproteins. VLDL is converted in the bloodstream to low-density lipoprotein (LDL) and intermediate-density lipoprotein (IDL). VLDL particles have a diameter of 30–80 nm. VLDL transports endogenous products, whereas chylomicrons transport exogenous (dietary) products. In the early 2010s both the lipid composition and protein composition of this lipoprotein were characterised in great detail.
Hypercholesterolemia, also called high cholesterol, is the presence of high levels of cholesterol in the blood. It is a form of hyperlipidemia, hyperlipoproteinemia, and dyslipidemia.
Dyslipidemia is a metabolic disorder characterized by abnormally high or low amounts of any or all lipids or lipoproteins in the blood. Dyslipidemia is a risk factor for the development of atherosclerotic cardiovascular diseases (ASCVD), which include coronary artery disease, cerebrovascular disease, and peripheral artery disease. Although dyslipidemia is a risk factor for ASCVD, abnormal levels don't mean that lipid lowering agents need to be started. Other factors, such as comorbid conditions and lifestyle in addition to dyslipidemia, is considered in a cardiovascular risk assessment. In developed countries, most dyslipidemias are hyperlipidemias; that is, an elevation of lipids in the blood. This is often due to diet and lifestyle. Prolonged elevation of insulin resistance can also lead to dyslipidemia. Likewise, increased levels of O-GlcNAc transferase (OGT) may cause dyslipidemia.
Chylomicrons, also known as ultra low-density lipoproteins (ULDL), are lipoprotein particles that consist of triglycerides (85–92%), phospholipids (6–12%), cholesterol (1–3%), and proteins (1–2%). They transport dietary lipids from the intestines to other locations in the body. ULDLs are one of the five major groups of lipoproteins that enable fats and cholesterol to move within the water-based solution of the bloodstream. A protein specific to chylomicrons is ApoB48.
Combined hyperlipidemia is a commonly occurring form of hypercholesterolemia characterised by increased LDL and triglyceride concentrations, often accompanied by decreased HDL. On lipoprotein electrophoresis it shows as a hyperlipoproteinemia type IIB. It is the most commonly inherited lipid disorder, occurring in around one in 200 persons. In fact, almost one in five individuals who develop coronary heart disease before the age of 60 have this disorder.
Gemfibrozil, sold under the brand name Lopid among others, is a medication used to treat abnormal blood lipid levels. It is generally less preferred than statins. Use is recommended together with dietary changes and exercise. It is unclear if it changes the risk of heart disease. It is taken by mouth.
Intermediate-density lipoproteins (IDLs) belong to the lipoprotein particle family and are formed from the degradation of very low-density lipoproteins as well as high-density lipoproteins. IDL is one of the five major groups of lipoproteins that enable fats and cholesterol to move within the water-based solution of the bloodstream. Each native IDL particle consists of protein that encircles various lipids, enabling, as a water-soluble particle, these lipids to travel in the aqueous blood environment as part of the fat transport system within the body. Their size is, in general, 25 to 35 nm in diameter, and they contain primarily a range of triglycerides and cholesterol esters. They are cleared from the plasma into the liver by receptor-mediated endocytosis, or further degraded by hepatic lipase to form LDL particles.
A lacteal is a lymphatic capillary that absorbs dietary fats in the villi of the small intestine.
Apolipoproteins are proteins that bind lipids to form lipoproteins. They transport lipids in blood, cerebrospinal fluid and lymph.
Hyperlipidemia is abnormally high levels of any or all lipids or lipoproteins in the blood. The term hyperlipidemia refers to the laboratory finding itself and is also used as an umbrella term covering any of various acquired or genetic disorders that result in that finding. Hyperlipidemia represents a subset of dyslipidemia and a superset of hypercholesterolemia. Hyperlipidemia is usually chronic and requires ongoing medication to control blood lipid levels.
Apolipoprotein B (ApoB) is a protein that in humans is encoded by the APOB gene. It is commonly used to detect risk of atherosclerotic cardiovascular disease.
Lipid metabolism is the synthesis and degradation of lipids in cells, involving the breakdown and storage of fats for energy and the synthesis of structural and functional lipids, such as those involved in the construction of cell membranes. In animals, these fats are obtained from food and are synthesized by the liver. Lipogenesis is the process of synthesizing these fats. The majority of lipids found in the human body from ingesting food are triglycerides and cholesterol. Other types of lipids found in the body are fatty acids and membrane lipids. Lipid metabolism is often considered as the digestion and absorption process of dietary fat; however, there are two sources of fats that organisms can use to obtain energy: from consumed dietary fats and from stored fat. Vertebrates use both sources of fat to produce energy for organs such as the heart to function. Since lipids are hydrophobic molecules, they need to be solubilized before their metabolism can begin. Lipid metabolism often begins with hydrolysis, which occurs with the help of various enzymes in the digestive system. Lipid metabolism also occurs in plants, though the processes differ in some ways when compared to animals. The second step after the hydrolysis is the absorption of the fatty acids into the epithelial cells of the intestinal wall. In the epithelial cells, fatty acids are packaged and transported to the rest of the body.
Familial hypercholesterolemia (FH) is a genetic disorder characterized by high cholesterol levels, specifically very high levels of low-density lipoprotein cholesterol, in the blood and early cardiovascular diseases. The most common mutations diminish the number of functional LDL receptors in the liver or produce abnormal LDL receptors that never go to the cell surface to function properly. Since the underlying body biochemistry is slightly different in individuals with FH, their high cholesterol levels are less responsive to the kinds of cholesterol control methods which are usually more effective in people without FH. Nevertheless, treatment is usually effective.
Hepatic lipase (HL), also called hepatic triglyceride lipase (HTGL) or LIPC (for "lipase, hepatic"), is a form of lipase, catalyzing the hydrolysis of triacylglyceride. Hepatic lipase is coded by chromosome 15 and its gene is also often referred to as HTGL or LIPC. Hepatic lipase is expressed mainly in liver cells, known as hepatocytes, and endothelial cells of the liver. The hepatic lipase can either remain attached to the liver or can unbind from the liver endothelial cells and is free to enter the body's circulation system. When bound on the endothelial cells of the liver, it is often found bound to heparan sulfate proteoglycans (HSPG), keeping HL inactive and unable to bind to HDL (high-density lipoprotein) or IDL (intermediate-density lipoprotein). When it is free in the bloodstream, however, it is found associated with HDL to maintain it inactive. This is because the triacylglycerides in HDL serve as a substrate, but the lipoprotein contains proteins around the triacylglycerides that can prevent the triacylglycerides from being broken down by HL.
A lipid profile or lipid panel is a panel of blood tests used to find abnormalities in blood lipid concentrations. The results of this test can identify certain genetic diseases and can determine approximate risks for cardiovascular disease, certain forms of pancreatitis, and other diseases.
Remnant cholesterol, also known as remnant lipoprotein, is a very atherogenic lipoprotein composed primarily of very low-density lipoprotein (VLDL) and intermediate-density lipoprotein (IDL). Stated another way, remnant cholesterol is all plasma cholesterol that is not LDL cholesterol or HDL cholesterol, which are triglyceride-poor lipoproteins. However, remnant cholesterol is primarily chylomicron and VLDL, and each remnant particle contains about 40 times more cholesterol than LDL.