Research Article Details
| Article ID: | A07208 |
| PMID: | 32582754 |
| Source: | Front Nutr |
| Title: | PTEN: A Thrifty Gene That Causes Disease in Times of Plenty? |
| Abstract: | The modern obesity epidemic with associated disorders of metabolism and cancer has been attributed to the presence of "thrifty genes". In the distant past, these genes helped the organism to improve energy efficiency and store excess energy safely as fat to survive periods of famine, but in the present day obesogenic environment, have turned detrimental. I propose PTEN as the likely gene as it has functions that span metabolism, cancer and reproduction, all of which are deranged in obesity and insulin resistance. The activity of PTEN can be calibrated in utero by availability of nutrients by the methylation arm of the epigenetic pathway. Deficiency of protein and choline has been shown to upregulate DNA methyltransferases (DNMT), especially 1 and 3a; these can then methylate promoter region of PTEN and suppress its expression. Thus, the gene is tuned like a metabolic rheostat proportional to the availability of specific nutrients, and the resultant "dose" of the protein, which sits astride and negatively regulates the insulin-PI3K/AKT/mTOR pathway, decides energy usage and proliferation. This "fixes" the metabolic capacity of the organism periconceptionally to a specific postnatal level of nutrition, but when faced with a discordant environment, leads to obesity related diseases. |
| DOI: | 10.3389/fnut.2020.00081 |
| 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 |
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name |
|---|
| 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 | |
|---|---|---|---|---|---|---|---|
| D080 | Citrulline | Chemical drug | DB00155 | -- | -- | Under clinical trials | Details |
| D579 | Emfilermin | Miscellany | -- | adipocytes | Enhance lipid metabolism | Under investigation | 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 |