The recent knowledge regarding the mechanism of fat absorption in human body has been briefly discussed below:
Most dietary fat of either vegetable or animal origin comprises of triglycerides in which glycerol is combined in low-energy ester linkages with three fatty acids and the fatty acids are of even number of carbon atoms. Fatty acids are both saturated and unsaturated which are almost entirely palmitic and stearic in case of former and in case of the latter oleic and linoleic acids. These are long-chain fatty acids. Milk fat contains 3 -10% (C4 – C14 acids) contributing shorter-chain fatty acids.
Since fats are insoluble in water and immiscible in chyme, so fat neither is absorbed as such nor is digested by lipase (due to lack of contact with lipase) to fatty acid and glycerol for absorption. Emulsification of fat by different emulsifying agent is required for preparing it suitable for both digestion and absorption and this process (emulsification) possible in small intestine where bile salt and other agents are present.
Bile salts themselves are relatively weaker than the mixture of bile salts and a polar body—lecithin, lysolecithin or monoglycerides as emulsifying agent. The latter two are produced by the action of pancreatic lipase on lecithin or triglycerides. Thus the enzymic action tends to stabilize the emulsion.
So fat digestion and absorption do not occur in stomach significantly which is devoid of emulsifying agent but natural (milk fat) or artificial emulsions are digested in the stomach. Recent studies account for many aspects of fat absorption better than previous supposition.
Aspects of Fat Absorption:
It has been observed that:
(1) Fatty acid is absorbed more readily than any other components, i.e., triglycerides, I-monoglycerides, 2-monoglycerides, diglycerides and free fatty acids (which are formed in the sample collected near- the duodeno-jejunal junction) and
(2) The hydrolysis occurring in the lumen is faster than the absorption of free fatty acid.
(3) There is spontaneous migration of fatty acids from one alcohol group to another in the glycerol.
The chief products of luminal hydrolysis of triglycerides are 2-monoglycerides and free fatty acid. Glycerol and 1-monoglycerides are quantitatively less important while fat is undergoing digestion and absorption. The fat is distributed among the emulsified fat droplets, micells (small), hydrated polymolecular aggregates and molecular solution. Micells of intestine contain three major components as bile salts, monoglycerides and fatty acids.
The salts spontaneously aggregate with monoglycerides and form micells when the concentration of bile salts attains a certain value known as critical micellar concentration. Since the concentration of conjugated bile salts remains always higher than the critical micellar concentration (at ordinary circumstances), the monoglycerides rapidly form micells as soon as they are liberated from triglycerides by lipase actively with bile salt.
As the micelle once formed it dissolves free fatty acid, cholesterol and fat-soluble vitamins and dissolution varies directly up to a limit with the amount of monoglyceride contained in it. But the unconjugated bile salt has got higher critical micellar concentration for which fat absorption is inhibited when bile salts are deconjugated in the gut.
The inhibition of absorption of fat (due to de-conjugation) is for the inability of micellar solution at this condition of holding monoglycerdies and free fatty acids liberated from lipolysis and thereby these are precipitated and become unavailable for absorption.
Lipid molecules in solution can diffuse into the epithelial cells through its lipoprotein membrane. So the metabolic machinery contained in the endoplasmic reticulum of the cell takes up monoglycerides and free fatty acid and rapidly synthesizes them into triglycerides. Diffusion gradient from lumen to cell down which free fatty acid and monoglycerides flow is present till the completion of absorption.
The gradient is produced by immediate replacement of monoglycerides and free fatty acids in the solution from the micellar phase as they leave the luminal solution and consequently the luminal solution remains saturated with free fatty acid and monoglycerides. Of the fat digestion products, the monoglycerides and fatty acids are separated from micells to be absorbed in the duodenum and jejunum and conjugated bile salts only in the terminal ileum.
The bile salts being insoluble in the cell membrane (due to their charge) must be actively transported. The rate of their absorption is proportional to their solubility and hence the more soluble monoglycerides are absorbed first and then follow other substances in the order of their solubility, viz., long-chain fatty acid, cholesterol, short and medium-chain fatty acids.
And the triglycerides of these acids are absorbed without passing through the micellar phase since they are relatively solution as well as in the cell membrane. Fat aggregation does not take place in the space between the microvilli and endoplasmic reticulum when fat re-synthesis occurs. Lysolecithin enters into the mucosal cell as such and its base is separated there by phosphodiesterase and its fatty acid by lysophosphatidase and finally glycerol and phosphate are separated by non-specific phosphatase.
Within the cells monoglycerides without further hydrolysis (of long-chain fatty acid) are resynthesized to triglycerides or phospholipids. The shorter-chain fatty acid ester is hydrolised by lipase (intracellular) and not those of long-chain fatty acids, (i.e., dietary fat). Mucosal cells can synthesis long-chain fatty acid, i.e., stearic acid (C18) from acetic acid as well as palmitic acid (C16) to stearic acid (C18) with acetic acid.
Glycerol liberated in the lumen by hydrolysis of triglycerides is partly oxidized in mucosal cell to CO2 and partly goes to liver for its conversion to glycogen and remaining is utilized in the re-synthesis of triglycerides. The glycerol required for the re-synthesis of triglycerides is also derived from glucose (glycolytic path). Resynthesized fat is absorbed into the lymph.
Intracellular Fat Transport:
After re-synthesis, the fats are accumulated more in the apical cells of the tip of villi than at the sides and they are restricted in the supranuclear part of the cell. It appears first as discrete particles in the endoplasmic reticulum. Microsomes derived from the reticulum contain enzymes which resynthesize triglycerides.
So fat is seen to be deposited in the reticulum. Re-synthesis and absorption take place simultaneously. The entire reticulum is filled with fat droplets and then the fat moves to the supranuclear part of the cell acquiring along its way an envelope of phospholipid and protein and finally they are expelled from the sides of the cell at or below the level of the nucleus.
Chylomicron:
Droplets of fat known as chylomicron is formed (aggregation of fat molecules) before the delivery of resynthesized fat into lymph.
The droplets are enclosed in a membrane, composed of small amount of protein, free cholesterol and saturated triglycerides in a monolayer of phospholipid. The fat in the chylomicron reflects the composition of ingested fat (dietary) partly since long-chain fatty acids of the dietary fat are added to mucosal cells for re-synthesis whereas most of short and medium-chain fatty acids and some glycerol are shunted to portal blood. Water-soluble components of fat diffuse into capillaries of the villi which are fenestrated.
The gap in the fenestra formed by an uninterrupted basement membrane envelope the endothelium and the fenestrae are possible gateway for entry of water-soluble compounds into the capillary blood Chylomicron cannot enter the fenestrae due to its particle size. It enters the lacteals through open channels existing between interstitial spaces and the lymphatic lumen. Although the endothelial wall of lacteals is relatively thick but there is absence of enveloping basement membrane and presence of intercellular space. The fat droplets pass through these spaces.
(The cells forming the walls of the lacteal contain many vesicles which may be capable of carrying fat droplets across them due to their pinocytotic property.)