Lipase inhibitor | |
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Drug class | |
Class identifiers | |
ATC code | A08AB |
Mode of action | Inhibits gastric lipase and pancreatic lipase |
Legal status | |
In Wikidata |
Lipase inhibitors are substances used to reduce the activity of lipases found in the intestine. Lipases are secreted by the pancreas when fat is present. The primary role of lipase inhibitors is to decrease the gastrointestinal absorption of fats. Fats then tend to be excreted in feces rather than being absorbed to be used as a source of caloric energy, and this can result in weight loss in individuals. [1] These inhibitors could be used for the treatment of obesity, which can subsequently lead to Type 2 diabetes and cardiovascular diseases if not managed. An example of a lipase inhibitor is orlistat. [2]
Lipase inhibitors may affect the amount of fat absorbed, yet they do not block the absorption of a particular type of fat. [1] Likewise, lipase inhibitors are not absorbed into the bloodstream. Lipase inhibitors bind to lipase enzymes in the intestine, [2] thus preventing the hydrolysis of dietary triglycerides into monoglycerides and fatty acids. [3] This then reduces the absorption of dietary fat. [2] Lipase inhibitors covalently bond to the active serine site on lipases. This covalent bond is strong, meaning the lipase inhibitor tends to remain attached to the lipase. [4] Studies have shown that lipase inhibitors work optimally when 40% of an individual's daily caloric intake is obtained from fat. [1] [ clarification needed ] Orlistat tends to block absorption of 30% of total fat intake from a meal, as orlistat passes out of the digestive tract more rapidly than fat does. [2]
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Lipase inhibitors can be found naturally in plants and can also be produced as pharmaceutical drugs. Some lipase inhibitors have been identified in Panax ginseng . [5] [6] Some active compounds with chalcone scaffold found in Glycyrrhiza glabra, Cassia mimosoides, Glycyrrhiza uralensis, Boesenbergia rotunda, apples and Morus alba also had strong effect against lipase. Caffeine, theobromine and theophylline were also supposed as lipase inhibitors although they are still controversial. [7]
Lipase inhibitors can cause side effects, including oily spotting, fecal incontinence, flatus with discharge [1] and abdominal cramping. [3] Additionally, a raise in blood pressure, dry mouth, constipation, headache, and insomnia have been reported. [3] Malabsorption of fat soluble vitamins may develop as a result of the impaired absorption of fat, which is required for the transportation of these vitamins across the intestine to reach the blood. [4] Since lipase inhibitors are not absorbed in the intestine, and consequently not circulating in the blood, information about alternative side effects such as the modulation[ clarification needed ] of the gastrointestinal tract is unobtainable. [1] Generally, side effects can be controlled by reducing the consumption of dietary fats. Overall, orlistat has been considered to be safer than other anti-obesity drugs. [2]
Because lipase inhibitors interfere with the absorption of fat, they can also prevent the absorption of fat-soluble vitamins. It is recommended that multi-vitamins are taken along with lipase inhibitors, so vitamin deficiency doesn't occur. [8]
Fructose, or fruit sugar, is a ketonic simple sugar found in many plants, where it is often bonded to glucose to form the disaccharide sucrose. It is one of the three dietary monosaccharides, along with glucose and galactose, that are absorbed by the gut directly into the blood of the portal vein during digestion. The liver then converts most fructose and galactose into glucose for distribution in the bloodstream or deposition into glycogen.
Dietary fiber or roughage is the portion of plant-derived food that cannot be completely broken down by human digestive enzymes. Dietary fibers are diverse in chemical composition and can be grouped generally by their solubility, viscosity and fermentability which affect how fibers are processed in the body. Dietary fiber has two main subtypes: soluble fiber and insoluble fiber which are components of plant-based foods such as legumes, whole grains, cereals, vegetables, fruits, and nuts or seeds. A diet high in regular fiber consumption is generally associated with supporting health and lowering the risk of several diseases. Dietary fiber consists of non-starch polysaccharides and other plant components such as cellulose, resistant starch, resistant dextrins, inulin, lignins, chitins, pectins, beta-glucans, and oligosaccharides.
Coenzyme Q10 (CoQ10) also known as ubiquinone, is a naturally occurring biochemical cofactor (coenzyme) and an antioxidant produced by the human body. It can also be obtained from dietary sources, such as meat, fish, seed oils, vegetables, and dietary supplements. CoQ10 is found in many organisms, including animals and bacteria.
Digestion is the breakdown of large insoluble food compounds into small water-soluble components so that they can be absorbed into the blood plasma. In certain organisms, these smaller substances are absorbed through the small intestine into the blood stream. Digestion is a form of catabolism that is often divided into two processes based on how food is broken down: mechanical and chemical digestion. The term mechanical digestion refers to the physical breakdown of large pieces of food into smaller pieces which can subsequently be accessed by digestive enzymes. Mechanical digestion takes place in the mouth through mastication and in the small intestine through segmentation contractions. In chemical digestion, enzymes break down food into the small compounds that the body can use.
Orlistat, sold under the brand name Xenical among others, is a medication used to treat obesity. Its primary function is preventing the absorption of fats from the human diet by acting as a lipase inhibitor, thereby reducing caloric intake. It is intended for use in conjunction with a healthcare provider-supervised reduced-calorie diet.
Olestra is a fat substitute food additive that adds no metabolizable calories to products. It has been used in the preparation of otherwise high-fat foods, thereby lowering or eliminating their fat content.
The bile acid sequestrants are a group of resins used to bind certain components of bile in the gastrointestinal tract. They disrupt the enterohepatic circulation of bile acids by combining with bile constituents and preventing their reabsorption from the gut. In general, they are classified as hypolipidemic agents, although they may be used for purposes other than lowering cholesterol. They are used in the treatment of chronic diarrhea due to bile acid malabsorption.
Gastric bypass surgery refers to a technique in which the stomach is divided into a small upper pouch and a much larger lower "remnant" pouch, where the small intestine is rearranged to connect to both. Surgeons have developed several different ways to reconnect the intestine, thus leading to several different gastric bypass procedures (GBP). Any GBP leads to a marked reduction in the functional volume of the stomach, accompanied by an altered physiological and physical response to food.
Malabsorption is a state arising from abnormality in absorption of food nutrients across the gastrointestinal (GI) tract. Impairment can be of single or multiple nutrients depending on the abnormality. This may lead to malnutrition and a variety of anaemias.
Anti-obesity medication or weight loss medications are pharmacological agents that reduce or control excess body fat. These medications alter one of the fundamental processes of the human body, weight regulation, by: reducing appetite and consequently energy intake, increasing energy expenditure, redirecting nutrients from adipose to lean tissue, or interfering with the absorption of calories.
Steatorrhea is the presence of excess fat in feces. Stools may be bulky and difficult to flush, have a pale and oily appearance, and can be especially foul-smelling. An oily anal leakage or some level of fecal incontinence may occur. There is increased fat excretion, which can be measured by determining the fecal fat level.
Lingual lipase is a member of a family of digestive enzymes called triacylglycerol lipases, EC 3.1.1.3, that use the catalytic triad of aspartate, histidine, and serine to hydrolyze medium and long-chain triglycerides into partial glycerides and free fatty acids. The enzyme, released into the mouth along with the saliva, catalyzes the first reaction in the digestion of dietary lipid, with diglycerides being the primary reaction product. However, due to the unique characteristics of lingual lipase, including a pH optimum 4.5–5.4 and its ability to catalyze reactions without bile salts, the lipolytic activity continues through to the stomach. Enzyme release is signaled by autonomic nervous system after ingestion, at which time the serous glands under the circumvallate and foliate lingual papillae on the surface of the tongue secrete lingual lipase to the grooves of the circumvallate and foliate papillae, co-localized with fat taste receptors. The hydrolysis of the dietary fats is essential for fat absorption by the small intestine, as long chain triacylglycerides cannot be absorbed, and as much as 30% of fat is hydrolyzed within 1 to 20 minutes of ingestion by lingual lipase alone.
Vitamin E deficiency in humans is a very rare condition, occurring as a consequence of abnormalities in dietary fat absorption or metabolism rather than from a diet low in vitamin E. Collectively the EARs, RDAs, AIs and ULs for vitamin E and other essential nutrients are referred to as Dietary Reference Intakes (DRIs). Vitamin E deficiency can cause nerve problems due to poor conduction of electrical impulses along nerves due to changes in nerve membrane structure and function.
Enterostatin is a pentapeptide derived from a proenzyme in the gastrointestinal tract called procolipase. It reduces food intake, in particular fat intake, when given peripherally or into the brain.
Chylomicron retention disease is a disorder of fat absorption. It is associated with SAR1B. Mutations in SAR1B prevent the release of chylomicrons in the circulation which leads to nutritional and developmental problems. It is a rare autosomal recessive disorder with around 40 cases reported worldwide. Since the disease allele is recessive, parents usually do not show symptoms.
Antinutrients are natural or synthetic compounds that interfere with the absorption of nutrients. Nutrition studies focus on antinutrients commonly found in food sources and beverages. Antinutrients may take the form of drugs, chemicals that naturally occur in food sources, proteins, or overconsumption of nutrients themselves. Antinutrients may act by binding to vitamins and minerals, preventing their uptake, or inhibiting enzymes.
Cetilistat is a drug designed to treat obesity. It acts in the same way as the older drug orlistat (Xenical) by inhibiting pancreatic lipase, an enzyme that breaks down triglycerides in the intestine. Without this enzyme, triglycerides from the diet are prevented from being hydrolyzed into absorbable free fatty acids and are excreted undigested.
Management of obesity can include lifestyle changes, medications, or surgery. Although many studies have sought effective interventions, there is currently no evidence-based, well-defined, and efficient intervention to prevent obesity.
Lipase inhibitors belong to a drug class that is used as an antiobesity agent. Their mode of action is to inhibit gastric and pancreatic lipases, enzymes that play an important role in the digestion of dietary fat. Lipase inhibitors are classified in the ATC-classification system as A08AB . Numerous compounds have been either isolated from nature, semi-synthesized, or fully synthesized and then screened for their lipase inhibitory activity but the only lipase inhibitor on the market is orlistat . Lipase inhibitors have also shown anticancer activity, by inhibiting fatty acid synthase.
Intestinal bypass is a bariatric surgery performed on patients with morbid obesity to create an irreversible weight loss, when implementing harsh restrictions on the diets have failed. Jejunocolic anastomosis was firstly employed. Nonetheless, it led to some unexpected complications such as severe electrolyte imbalance and liver failure. It was then modified to jejunoileal techniques. Viewed as a novel form of treatment for obesity, many intestinal bypass operations were carried out in the 1960s and 1980s. Significant weight loss was observed in patients, but this surgery also resulted in several complications, for instance, nutritional deficiencies and metabolic problems. Due to the presence of surgical alternatives and anti-obesity medications, intestinal bypass is now rarely used.