Research Article Details
| Article ID: | A26386 |
| PMID: | 20553760 |
| Source: | Prog Lipid Res |
| Title: | Biosynthesis and bioavailability of long-chain polyunsaturated fatty acids in non-alcoholic fatty liver disease. |
| Abstract: | Non-alcoholic fatty liver disease (NAFLD) has a high occurrence in most countries. Recent studies estimate its prevalence to be near 30% in United States, Italian and Japanese general adult populations. NAFLD commonly presents along with obesity and insulin resistance (IR), pathologies that share with NAFLD metabolic and inflammatory components. These conditions, particularly NAFLD, are associated with alterations in the bioavailability of long-chain polyunsaturated fatty acids (LCPUFAs). In the human population, the bioavailability of LCPUFAs depends both on endogenous biosynthesis and diet amount of preformed LCPUFAs. However, the lower liver LCPUFAs product/precursor ratio namely (20:5n-3+22:6n-3)/18:3n-3, 20:4n-6/18:2n-6 present in common Western diets, makes critical an adequate pathway activity to ensure minimum bioavailability of LCPUFAs in most Western populations. The key step of this biosynthesis involves Δ5 and Δ6-desaturases, whose activities are altered in NAFLD. During the disease, the presence of molecular activators of these two enzymes does not correlate with the scarce LCPUFAS biosynthesis observed. The key to this apparent contradiction, or at least part of it, could be explained on the basis of the possible sensitivity of the desaturases to oxidative stress; a metabolic condition strongly linked to inflammatory pathologies such as NAFLD, obesity and IR and that, according to latest research, not only would be consequence but also possibly a cause of these diseases. The present review is focused on the relationship between NAFLD and the bioavailability of LCPUFAs, with special reference to the role that oxidative stress could play in the modulation of the liver fatty acid desaturase activity. |
| DOI: | 10.1016/j.plipres.2010.05.003 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S01 | Improve insulin resistance | insulin sensitizer; insulin resistance; glucose tolerance | Biguanide: increases 5-AMP activated protein kinase signaling; SGLT-2 inhibitor; Thiazalidinedione: selective PPAR-γ agonists; GLP-1 agonist | Metformin; Empagliflozin; Canagliflozin; Rosiglitazone; Pioglitazone; Liraglutide | Details |
| S04 | Anti-oxidative stress | oxidative stress | α-tocopherol: antioxidant | Vitamin E | Details |
| S05 | Anti-inflammatory | inflammatory | Bile acid; TNF-a inhibitor; Dual PPAR-α and -δ agonists; Toll-Like Receptor; (TLR)-4 antagonist; Caspase inhibitor; ASK-1 inhibitor | Ursodeoxycholic Acid; Pentoxifylline; Elafibranor; JKB-121; Emricasan; Selonsertib; | Details |
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I05 | 9352 | Type 2 diabetes mellitus | A diabetes that is characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both. A diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. http://en.wikipedia.org/wiki/Diabetes, http://en.wikipedia.org/wiki/Diabetes_mellitus_type_2 | disease of metabolism/inherited metabolic disorder/ carbohydrate metabolic disorder/glucose metabolism disease/diabetes/ diabetes mellitus | Details |
| I14 | 9970 | Obesity | An overnutrition that is characterized by excess body fat, traditionally defined as an elevated ratio of weight to height (specifically 30 kilograms per meter squared), has_material_basis_in a multifactorial etiology related to excess nutrition intake, decreased caloric utilization, and genetic susceptibility, and possibly medications and certain disorders of metabolism, endocrine function, and mental illness. https://en.wikipedia.org/wiki/Obesity | disease of metabolism/acquired metabolic disease/ nutrition disease/overnutrition | Details |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D328 | Serine | Chemical drug | DB00133 | SRR | Improve insulin resistance | Under clinical trials | Details |
| D504 | Polyunsaturated Fatty Acids | Supplement | -- | -- | -- | Under clinical trials | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |