Research Article Details
| Article ID: | A43094 |
| PMID: | 32586106 |
| Source: | Antioxid Redox Signal |
| Title: | Phospholipase D as a Potential Modulator of Metabolic Syndrome: Impact of Functional Foods. |
| Abstract: | Significance: Cardiometabolic disorders (CMD) are composed of a plethora of metabolic dysfunctions such as dyslipidemia, nonalcoholic fatty liver disease, insulin resistance, and hypertension. The development of these disorders is highly linked to inflammation and oxidative stress (OxS), two metabolic states closely related to physiological and pathological conditions. Given the drastically rising CMD prevalence, the discovery of new therapeutic targets/novel nutritional approaches is of utmost importance. Recent Advances: The tremendous progress in methods/technologies and animal modeling has allowed the clarification of phospholipase D (PLD) critical roles in multiple cellular processes, whether directly or indirectly via phosphatidic acid, the lipid product mediating signaling functions. In view of its multiple features and implications in various diseases, PLD has emerged as a drug target. Critical Issues: Although insulin stimulates PLD activity and, in turn, PLD regulates insulin signaling, the impact of the two important PLD isoforms on the metabolic syndrome components remains vague. Therefore, after outlining PLD1/PLD2 characteristics and functions, their role in inflammation, OxS, and CMD has been analyzed and critically reported in the present exhaustive review. The influence of functional foods and nutrients in the regulation of PLD has also been examined. Future Directions: Available evidence supports the implication of PLD in CMD, but only few studies emphasize its mechanisms of action and specific regulation by nutraceutical compounds. Therefore, additional investigations are first needed to clarify the functional role of nutraceutics and, second, to elucidate whether targeting PLDs with food compounds represents an appropriate therapeutic strategy to treat CMD. Antioxid. Redox Signal. 34, 252-278. |
| DOI: | 10.1089/ars.2020.8081 |
| 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 |
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name |
|---|
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I13 | 3146 | Lipid metabolism disorder | An inherited metabolic disorder that involves the creation and degradation of lipids. http://en.wikipedia.org/wiki/Lipid_metabolism | disease of metabolism/ inherited metabolic disorder | Details |
| I12 | 10763 | Hypertension | An artery disease characterized by chronic elevated blood pressure in the arteries. https://en.wikipedia.org/wiki/Hypertension, https://www.ncbi.nlm.nih.gov/pubmed/24352797 | disease of anatomical entity/ cardiovascular system disease/vascular disease/ artery disease | Details |
| 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 |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D273 | Phosphatidylcholine | Chemical drug | DB15834 | -- | -- | Under clinical trials | Details |
| D083 | CLA | Chemical drug | DB01211 | KCNH2; SLCO1B1; SLCO1B3 | -- | Under clinical trials | Details |
| D075 | Choline | Supplement | DB00122 | PLD2 product of; PLD1 product of | -- | Under clinical trials | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |