An Overview of Molecular Nutrition
Nicole M. Farmer, Andres Victor Ardisson Korat in Cooking for Health and Disease Prevention, 2022
Once in the stomach, gastric lipase, amongst other digestive enzymes, is released. However, gastric lipase is responsible for only the initial and minimal breakdown of ingested fats. The large majority of fat digestion does not occur in the stomach, but later on in the small intestine. Once released from the food matrix, fat is now bound to bile salts to undergo its main form of digestion in the small intestine. Pancreatic lipase works to break down triglyceride fats into monoglycerides and fatty acids. The efficient activity of the lipase is dependent on the presence of bile salts on fat droplets. Multiple bile salts with the complexed triglyceride components spontaneously form micelles. Micelles then enter enterocytes where the bile is broken down and chylomicrons are packaged and extruded from the basolateral enterocyte wall to enter the lymphatics. This is the mechanism for absorption of triglycerides which represent 90% of dietary fat. Dietary cholesterol undergoes a similar process except it requires a transport protein in order to enter the enterocyte. Lastly, MCTs, such as coconut oil, when extruded from the enterocyte go directly into the blood stream, by passing the lymphatic system. Therefore, MCTs are suspected of having a favorable metabolic profile.
Anti-Obesity Potential of Indian Traditional Medicinal Plants and Their Phytochemicals
Parimelazhagan Thangaraj in Medicinal Plants, 2018
Pancreatic lipase plays a key role in the efficient digestion of triglycerides (Lowe 2002). It is secreted into the duodenum through the duct system of the pancreas and is responsible for the hydrolysis of 50–70% of total dietary fats. This enzyme has been widely used for the determination of the potential efficacy of natural products as anti-obese agents (Sugiyama et al. 2007). Orlistat is currently the only clinically approved drug for obesity management in Europe. This molecule acts by inhibiting pancreatic lipase activity and the reduction of triglyceride absorption, and its long-term administration accompanying an energy restricted diet results in weight loss (Neovius et al. 2008). Reduction on intestinal lipid digestion has been related to a decrease in the intra-abdominal fat content. Thus, this compound is associated with a small, but statistically significant weight loss of about 3% more than diet alone in overweight and obese people.
The digestive system
Laurie K. McCorry, Martin M. Zdanowicz, Cynthia Y. Gonnella in Essentials of Human Physiology and Pathophysiology for Pharmacy and Allied Health, 2019
Intact triglycerides are too large to be absorbed. Therefore, pancreatic lipase acts on the lipid droplets to hydrolyze the triglyceride molecules into monoglycerides and free fatty acids. These constituent molecules are water-insoluble and would tend to float on the surface of the aqueous chyme. Therefore, they must be transported to the absorptive surface. This process is carried out by micelles, which are sphere-like structures formed by the amphipathic bile salts. The bile salts associate with each other such that the polar region of the molecules orient outward, making them water-soluble. The nonpolar region faces inward, away from the surrounding water. The monoglycerides and free fatty acids are carried in this interior region of the micelle. Upon reaching the brush border of the absorptive cells, the monoglycerides and free fatty acids leave the micelles and enter the cells by simple diffusion. Because they are nonpolar, these molecules move passively through the lipid bilayer of the cell membrane. This process takes place primarily in the jejunum and proximal ileum. The bile salts are absorbed in the distal ileum by way of either passive diffusion or secondary active transport.
Targeting the intestinal lymphatic system: a versatile path for enhanced oral bioavailability of drugs
Published in Expert Opinion on Drug Delivery, 2018
Renuka Suresh Managuli, Sushil Yadaorao Raut, Meka Sreenivasa Reddy, Srinivas Mutalik
The mechanism involved in uptake of lipid formulations into ILS is not yet clearly established. However, it has been hypothesized that these lipid formulations like diet lipid stimulate the synthesis of chylomicron and the drug get associated with these chylomicrons leading to its uptake into ILS via lacteal. The detailed mechanism involved in lipid absorption through ILS from the intestinal lumen is as follows: The lipids in the small intestine are acted upon by bile salt and pancreatic lipase which are mixed with the chyme. Bile acids by virtue of their amphiphillic nature, promote the emulsification of lipids, wherein hydrophobic part of bile acid interacts with lipid bilayer and hydrophilic part shields the surface of large lipid aggregates leading to its breakdown into smaller version. Pancreatic lipase then acts on the surface of triglyceride and breaks into monoglyceride and fatty acids. Unless the triglycerides are broken into monoglycerides and fatty acids, there will be reduced absorption of lipid and this strategy is used in the treatment of obesity using drugs such as ‘Orlistat’ which inhibits pancreatic lipase.
Strong inhibitory activities and action modes of lipopeptides on lipase
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2020
Mei-chun Chen, Tian-tian Liu, Jie-ping Wang, Yan-ping Chen, Qing-xi Chen, Yu-jing Zhu, Bo Liu
Dietary and lifestyle modifications such as calorie restriction and physical exercises are the common strategies adopted to control body weight; further, these methods have limited anti-obesity effects4. It has previously been reported that lipase inhibition is a potential strategy for counteracting obesity. Digestive lipase hydrolyses non-absorbable dietary triglycerides to smaller absorbable molecules of monoglycerides and free fatty acids, which are absorbed by the intestine. Inhibiting digestive lipase can reduce intestinal fat absorption5–7. Human pancreatic lipase is the main enzyme in intestinal digestion of dietary fats in the human digestive system. To date, a wide variety of natural products have been used as pancreatic lipase inhibitors, which originate from plants and metabolites of microorganisms. These include lipstatin, panclicins, saponins, polyphenols, flavonoids, caffeine, chitin, chitosan, etc5. The lipase inhibitor orlistat is the only one obesity-treatment drug currently available in the market, which reduces intestinal fat absorption via inhibition of pancreatic lipase; however, it has been reported to cause certain side effects, e.g. oily stools, oily spotting, and flatulence1,8. Some polyphenol compounds have been reported to have potential adverse effects on microorganisms and animal at high concentrations9,10. Thus, there is still a need to explore safe and effective anti-obesity drugs.
Rationale utilization of phospholipid excipients: a distinctive tool for progressing state of the art in research of emerging drug carriers
Published in Journal of Liposome Research, 2023
Koilpillai Jebastin, Damodharan Narayanasamy
Oral LBDDS are premised on the principle of delivering an API to the GIT in a non-aqueous solution. Slow drug dissolution from solid dosage forms, which is frequent with poorly water-soluble medications, is avoided by providing the drug in a solubilized condition. LBDDS are subjected to GI processing after gastric emptying, which includes dispersion, digestion, and bile mixing (Porter et al. 2007). Drug products containing triglycerides (TG) are disseminated in the stomach after ingestion, where gastric lipase begins lipid digestion. Mechanical mixing in the stomach, together with amphiphilic moieties derived from the LBDDS or initial lipid digestion, aids in the emulsification of lipids before they enter the duodenum (Figure 9). The presence of exogenous lipids in the latter is the stimulus that causes the gallbladder to secrete bile fluid and the pancreas to secrete pancreatic fluid. Pancreatic lipase and its cofactor co-lipase complete the breakdown of ingested glycerides into di-glyceride, monoglyceride, and fatty acid in the small intestine (Dahan and Hoffman 2008, Bolko et al. 2014).
Related Knowledge Centers
- Digestive Enzyme
- Enzyme
- Hydrolysis
- Isozyme
- Lipase
- Molecule
- Pancreas
- Protein Family
- Low-Density Lipoprotein
- Fat