Fatty acids are divided into short-chain fatty acids (4 carbon and below), medium-chain fatty acids (6-12 carbon), and long-chain fatty acids (14 carbon and above) according to the length of the carbon chain.Fatty acids below 6 carbon are poorly distributed in nature, and the metabolic pathways of 12-carbon lauric acids and long-chain fatty acids are similar, so the typical medium-chain fatty acids only include fatty acids of 8-10 carbon.

Medium-chain fatty acids, long-chain fatty acids and glycerol constitute triglycerides, i.e. medium-chain triglycerides (MCT) and long-chain triglycerides (LCT), and the digestion, absorption and metabolism of these two fatty acids are very different.
Figure 1 Digestion, absorption and metabolism of LCT and MCT.

LCT

1. Oral cavity
After LCT enters the mouth, salivary lipase will cause hydrolysis of triglycerides, and the fatty acids in the 3rd position of triglycerides will be hydrolyzed to produce 1,2-glycerol diesters and free fatty acids. However, in human beings, especially in adults, this kind of hydrolysis is extremely small, and almost all of the triglycerides pass through the esophagus to reach the stomach directly.

2. Gastric
Gastric lipase, like salivary lipase, hydrolyzes only a small fraction of the triglycerides, so that in the stomach LCT is still mainly in the form of triglycerides. Through the peristaltic action of the stomach, fats and oils are emulsified together with other foodstuffs and slowly pass through the pylorus into the duodenum in the form of small pieces.

3. Small intestine
Hydrolysis of triglycerides mainly takes place in the duodenum. Under the action of pancreatic lipase, one molecule of triglyceride is hydrolyzed into two molecules of free fatty acid and one molecule of 2-glycerol monoester. Next, free fatty acids and monoglycerides (and phospholipids, cholesterol, etc.) form a mixed microcluster with bile acids in the digestive juices, and the mixed microcluster is absorbed by the jejunum in the upper part of the small intestine with the help of the villi of the small intestine; the bile acids in the mixed microcluster are not absorbed immediately, but only the lipid fraction. After absorption in the small intestine, in the epithelial cells of the small intestine, free fatty acids and monoglycerides are re-esterified to triglycerides, which then form celiac particles together with phospholipids and cholesterol esters into the lymphatics.

4. Lymph and blood
Celiac particles pass through the lymphatic vessels and merge with blood at the subclavian vein, thus entering the blood circulation. Some of the triglycerides in the blood are hydrolyzed to 2-glycerol monoesters and free fatty acids under the action of lipoprotein lipase (LPL) and are stored in tissues and muscles throughout the body, while the unhydrolyzed triglycerides enter the liver.

5. Liver
The liver performs fat mobilization when the body needs energy. Triglycerides are hydrolyzed and β-oxidized, and are completely broken down into carbon dioxide, water, and energy.

Table 1 Comparison of LCT and MCT metabolism

MCT

1. Oral
Salivary lipase in the oral cavity hydrolyzes the 3 fatty acids of MCT much faster than LCT, so MCT is partially hydrolyzed in the oral cavity.

2. Stomach
Most of MCT is hydrolyzed to glycerol and free fatty acids in the stomach, because MCT is hydrophilic, it is easier to hydrolyze.

3. Small intestine
Most of the MCT enters the duodenum as free fatty acids, so pancreatic lipase is not required. In addition, MCT is highly hydrophilic and does not require the participation of bile acids to form mixed microclusters. Like glucose and amino acids, which are the breakdown products of sugars and proteins, MCT can be directly transported to the liver through the portal vein. Recently, it has been shown that MCT, which is not hydrolyzed in the stomach, can be absorbed directly into the small intestine in the form of triglycerides. Since pancreatic lipase and bile acids are not required, MCT is suitable for patients with digestive disorders.

4. Liver
After MCT reaches the liver through the portal vein, it undergoes rapid β-oxidation and is eventually broken down into energy, carbon dioxide and water.

The β-oxidation process of MCT and LCT is also different. Fatty acid oxidation takes place in mitochondria, and LCT requires the assistance of lipoyl coenzyme A synthetase, carnitine and carnitine lipoyltransferase (CPT-1, CPT-2, CPT-1 is the rate-limiting enzyme for β-oxidation) to enter the mitochondrial outer and inner membranes, whereas MCT forms the medium-chain fatty acid, lipoyl coenzyme A, which can pass directly through the mitochondrial membrane to undergo β-oxidation in response to the action of lipoyl coenzyme A. Therefore, MCT has a faster β-oxidation rate than LCT generates energy much faster.

After MCT becomes medium-chain fatty acid lipoyl coenzyme A, part of it is synthesized by the liver into triglycerides, phospholipids and cholesteryl esters, etc., but this proportion is much less than that of LCT. Most of it is β-oxidized in the mitochondria to acetyl coenzyme A, which further enters the tricarboxylic acid cycle, ketogenesis, fatty acid synthesis, or cholesterol synthesis. Thus, the final products of MCT in the body are carbon dioxide, water, ketone bodies (acetone, acetoacetate, β-hydroxybutyrate), cholesterol, or entry into the tricarboxylic acid cycle to produce citric acid for re-synthesis of fat.