Learn More About Triglycerides

Triglyceride (TG) is a fat molecule formed by long-chain fatty acids and glycerol. Triglycerides are the most abundant lipids in the body, and most tissues can use triglyceride breakdown products to supply energy, while liver, fat and other tissues can also synthesize triglycerides and store them in adipose tissue.

Triglyceride (TG) is an organic compound that is produced by esterifying three hydroxyl groups of glycerol with three fatty acid molecules to produce glycerides. It is a non-polar substance, stored in the body in non-hydrated form, and is the largest energy substance in the body in terms of reserves and production capacity. Plant-based triacylglycerols are mostly oils, and animal-based triacylglycerols are mostly lipids. Solid and liquid triacylglycerols are collectively referred to as fats and oils.
In medium and low intensity exercise, its breakdown provides most of the energy required by exercising muscles.

TG, also known as neutral fat, consists of 3 molecules of fatty acids and 1 molecule of glycerol esterified and is the main source of energy in the body. tG is in the core of lipoproteins and is transported as lipoproteins in the blood. In addition to TG, diglycerides, monoglycerides (the sum of which is less than 3% of TG) and free glycerol (FG) are also present in peripheral blood. Of the various lipoproteins, celiac (CM), very low density lipoprotein (VLDL) and their remnants are high in TG and are collectively referred to as TG-rich lipoproteins (TRL), also known as remnant-like lipoproteins (RLP). A growing body of clinical and experimental evidence suggests that TRL plays an important role in the etiology of AS and may play a role in the early stages of AS lesions.

Where do triglycerides come from?

There are two main sources of plasma triglycerides.

① exogenous: fats taken from food in the intestine, absorbed by the intestinal mucosa under the action of bile acids and lipases, and triglycerides are synthesized in the epithelial cells of the intestinal mucosa.

②Endogenous: The triglycerides synthesized by the body itself are mainly in the liver, followed by adipose tissue. The main function of triglycerides is to supply and store energy, and also to fix and protect the internal organs. Serum triglyceride measurement is a routine part of lipid analysis.

What should be the value of triglycerides?

Normal reference values for serum triglycerides: 0.45-1.69 mmol/L. Fasting (12 hours fasting) triglycerides below 1.70 mmol/L are considered appropriate; 1.70-2.25 mmol/L is considered borderline elevated; ≥2.26 mmol/L is considered elevated. The level values vary from region to region.

Increased and decreased triglyceride levels

1. Increased: Triglycerides are a risk factor for cardiovascular disease. Serum triglyceride levels are influenced by age, gender and diet. Increased serum triglycerides can be seen in familial hypertriglyceridemia, high dietary triglycerides and secondary to certain diseases such as diabetes mellitus, hypothyroidism, nephrotic syndrome and pancreatitis, atherosclerosis, glycogen storage disease, etc.

2. Decreased: seen in hyperthyroidism, reduced adrenocortical function, severe hepatic hypofunction, chronic obstructive pulmonary disease, cerebral infarction, malnutrition, congenital alpha-beta lipoproteinemia, etc.

Triglyceride test recommendations

1. Serum triglyceride levels are influenced by lifestyle habits, diet, age, etc. and fluctuate widely within and between individuals.

2. Eat as little lipid-containing food as possible 2 to 3 days before blood collection, and draw blood on an empty stomach for 12 hours to exclude and reduce the influence of diet.

Triglyceride metabolism

Catabolism

Triglycerides in adipose tissue are broken down to produce glycerol and fatty acids under the action of a series of lipases, and released into the blood for use by other tissues in a process called: lipid mobilization.

In this series of hydrolysis, triglyceride lipase, which catalyzes the hydrolysis of triglycerides to produce diglycerides, is the rate-limiting enzyme of lipid mobilization, and its activity is regulated by many hormones called hormone sensitive lipase (HSL). Glucagon, epinephrine and norepinephrine interact with adipocyte membrane receptors to activate adenylate cyclase, which increases intracellular cAMP levels, which in turn activates cAMP-dependent protein kinase, which phosphorylates HSL and activates it to promote triglyceride hydrolysis, and these hormones that promote lipid mobilization are called lipolytic hormones. Insulin and prostaglandins, which have the opposite effect of the above hormones, can inhibit lipid mobilization and are called antilipolytic hormones.

The fatty acids produced by lipid mobilization are released into the blood and bound to albumin to form lipoalbumin for transport to other tissues for use. Glycerol is transported to the liver, where it is catalyzed by glycerol kinase to produce glycerol 3-phosphate, which is broken down by the glycolytic pathway or used for gluconeogenesis. Adipose and muscle tissues lack glycerol kinase and are unable to utilize glycerol.

Anabolism

The body can use glycerol, sugar, fatty acids and monoglycerides as raw materials to synthesize triglycerides via the phosphatidic acid pathway and the monoglyceride pathway.

1. Monoglyceride pathway

Triglycerides are produced by esterification of monoglycerides with lipid acyl CoA under the action of lipid acyltransferase as a starting material.

2. Phosphatidic acid pathway

Phosphatidic acid, or 3 phosphate-1,2-glycerol diester, is a common precursor for the synthesis of glycerol-containing lipids. The intermediate product of glycolysis, dihydroxyacetone phosphate, is reduced by glycerophosphate dehydrogenase to produce α-phosphoglycerol (or 3-phosphoglycerol); free glycerol can also be catalyzed by glycerol kinase to produce α-phosphoglycerol (because adipose and muscle tissues lack glycerol kinase, they cannot use the radical glycerol). 1,2 diglyceride is phosphatidic acid. In addition, dihydroxyacetone phosphate may not be converted to α-phosphoglycerol, but is first esterified and then reduced to form lysophosphatidic acid, which is then synthesized by esterification.

Triglyceride metabolism process

Phosphatidic acid is converted to triglyceride by hydrolysis and release of inorganic phosphate under the action of phosphatidic acid phosphatase, which is the precursor of triglyceride and only needs esterification to produce triglyceride.

The three fatty acids contained in triglycerides can be the same or different, and can be saturated or unsaturated fatty acids.

The rate of triglyceride synthesis can be altered by hormonal influences, such as insulin, which promotes the conversion of sugar to triglycerides. In diabetic patients due to insufficient secretion or failure of insulin action, not only is glucose not well utilized, but also glucose or certain amino acids are not available for fatty acid synthesis, and instead they show an increased rate of fat oxidation and excessive ketone body production, with the result that patients lose weight. In addition, glucagon and adrenocorticotropic hormone also affect the synthesis of triglycerides.

Where are triglycerides distributed?

Characteristics of triglyceride synthesis in different tissues

The synthesis of triglycerides in different tissues and cells has its own characteristics.

1) Liver　

The liver can synthesize triglycerides through the phosphatidic acid pathway using sugar, glycerol and fatty acids as raw materials. The sources of fatty acids are fatty acids from lipid mobilization, fatty acids generated by the transformation of sugar and amino acids and exogenous fatty acids from food (short and medium chain fatty acids from digestion and absorption of fat from food into the liver through the blood, fatty acids generated from the decomposition of fat in residual particles of celiac particles)

Liver cells contain about 4-7% lipids, of which triglycerides account for about 1/2. Excessive triglyceride content can cause fatty liver. Under normal conditions, triglycerides synthesized by the liver form very low density lipoproteins together with phospholipids, cholesterol and apolipoproteins, which are secreted into the blood. If phospholipid synthesis is impaired or apolipoprotein synthesis is impaired, triglyceride transport out of the liver can be affected, causing fatty liver. In addition, if too much fatty acid enters the liver, the amount of triglyceride synthesis exceeds the ability to synthesize apolipoproteins, which can also cause fatty liver

2) Adipose tissue　

The synthesis of triglycerides in adipose tissue is basically the same as that in the liver, the difference between the two is that adipose tissue cannot use glycerol, but only alpha-phosphoglycerol provided by sugar decomposition; adipose tissue can store triglycerides in large quantities

3) Small intestinal mucosal epithelial cells　

There are two pathways for the synthesis of triglycerides by the mucosal epithelium of the small intestine. After a meal, triglycerides in food are hydrolyzed to produce free fatty acids and monoglycerides. After absorption, triglycerides are synthesized via the glycerol ester pathway. These triglycerides are involved in the composition of celiac particles. This pathway is the main feature of triglyceride synthesis in the small intestinal mucosa. In the case of starvation, the small intestinal mucosa can also synthesize triglycerides via the phosphatidic acid pathway using sugar, glycerol and fatty acids as raw materials, and this part of triglycerides is involved in the composition of very low density lipoproteins. In this case, the synthesis of raw materials and processes are again similar to those of the liver　

What is the disease of too high triglycerides?

Hypertriglyceridemia

Hypertriglyceridemia is a heterogeneous disorder of triglyceride protein synthesis and degradation.

• The normal triglyceride level: <l00mg/dL (1.13mmol/L) in children and <150mg/dL (1.7mmol/L) in adults
• The Critical hypertriglyceridemia: 250-500mg/dL (2.83-5.65mmol/L)
• The Definite hypertriglyceridemia: >500mg/dL (5.65mmol/L)
• The Physiology: triglycerides containing mainly lipoproteins as celiac particles: absorption of dietary fat by the intestine in the post-feeding state

Very low density lipoprotein (VLDL): endogenously synthesized in the liver from carbohydrates and fatty acids in the fasting state

Intermediate density lipoprotein (IDL): formed by the degradation of celiac particles and VLDL

Typing

Based on the type of lipoprotein, the following types are distinguished

Type I: Significantly elevated celiac particles, manifested by hypertriglyceridemia and mildly elevated cholesterol. It is often seen in childhood. It is often accompanied clinically by abdominal pain caused by pancreatitis, hepatosplenomegaly, rash xanthomas and retinal lipemia. There is no increased risk of atherosclerosis, and the cause can be primary (autosomal recessive) or secondary, such as SLE, gamma globulin dysplasia

Type IIA: elevated LDL. With hypercholesterolemia, see hypercholesterolemia

Type IIB: Elevated LDL and VLDL with hypercholesterolemia and hypertriglycerides. High risk of atherosclerosis. Primary causes include several genetic disorders and secondary causes include hypothyroidism, liver and kidney disease, porphyria, and multiple myeloma

Type III: elevated IDL (abnormal blood beta lipoproteins), manifested by high cholesterol and high triglycerides, most primary patients have abnormalities of the pure subunit of deoxyribonuclein Ez, secondary causes are hypothyroidism and gamma globulin dysplasia

Type IV: elevated VLDL with high triglycerides and mildly elevated cholesterol. Increased risk of atherosclerosis in some cases

Type V: elevated celiac and VLDL with markedly elevated triglycerides and high cholesterol, autosomal recessive due to LPL or apo-C defects, increased risk of atherosclerosis

Note: The above classification is intended to illustrate the disease only and rarely addresses heritability and pathogenesis. Plasma lipoproteins vary over time in any individual, a phenomenon that can be expected because of the precursor-producer relationship between the metabolism of VLDL and LDL and the role of diet on VLDL The same disease can lead to multiple different lipoprotein patterns, and multiple diseases can cause the same lipoprotein phenotype.

Diagnostic criteria for hyperlipidemia

Currently, hyperlipidemia is generally diagnosed in adults in China with fasting serum total cholesterol over 5.72 mmol/L and triglycerides over 1.70 mmol/L. Those with total cholesterol in the range of 5.2 to 5.7 mmol/L are referred to as borderline elevated.

Based on the results of serum total cholesterol, triglycerides and HDL-cholesterol measurements, hyperlipidemia is usually classified into four types as follows.

(1) Hypercholesterolemia: an increased serum total cholesterol level of more than 5.72 mmol/L and a normal triglyceride level, i.e., triglycerides <1.70 mmol/L.

(2) Hypertriglyceridemia: increased serum triglyceride level exceeding 1.70 mmol/L and normal total cholesterol level, i.e. total cholesterol <5.72 mmol/L.

(3) Mixed hyperlipidemia: increased serum total cholesterol and triglyceride levels, i.e., total cholesterol over 5.72 mmol/L and triglycerides over 1.70 mmol/L.

(4) HypoHDLemia: decreased serum high-density lipoprotein-cholesterol (HDL-cholesterol) level <9.0 mmol/L.

How to treat high triglycerides?

For patients with a clear cause of hypertriglyceridemia, treatment should be directed at the cause. Improve lifestyle first rather than taking oral medications first. Usually, after a period of dietary control and increased exercise, the triglyceride index can be reduced to normal levels in most patients. Those with severely elevated triglycerides (≥5.65 mmol/L) should be first treated with medications.

Lifestyle changes include the following.

① Weight control. Reducing body weight by 5%-10% in overweight or obese patients can reduce triglyceride levels by about 20%.

②Rational diet. By controlling total dietary calories, controlling the total amount of carbohydrates (including rice and noodles) and fat intake, and increasing the intake of vegetables and high-quality protein, triglyceride levels can be reduced by 20%-

③ Limiting alcohol consumption. Alcohol abuse is a common cause of elevated triglycerides, and those with severely elevated triglycerides should quit drinking immediately.

④ Moderate exercise. People with elevated triglycerides should do at least 30 minutes of moderate intensity aerobic exercise daily, at least 5 times a week, including brisk walking, cycling, stair climbing and other forms of exercise, and overweight or obese people should further increase the amount of exercise.

⑤ Quit smoking. Smoking not only raises triglyceride levels, but also increases the risk of serum hypertriglyceridemia to the body, and patients with hypertriglyceridemia should quit smoking.

References：

1. Triglyceride - Wikipedia

See also:

1. Cholesterol care