Research Article Details
| Article ID: | A33484 |
| PMID: | 25903417 |
| Source: | Handb Exp Pharmacol |
| Title: | Immune Cells and Metabolism. |
| Abstract: | Low-grade inflammation in the obese AT (AT) and the liver is a critical player in the development of obesity-related metabolic dysregulation, including insulin resistance, type 2 diabetes and non-alcoholic steatohepatitis (NASH). Myeloid as well as lymphoid cells infiltrate the AT and the liver and expand within these metabolic organs as a result of excessive nutrient intake, thereby exacerbating tissue inflammation. Macrophages are the paramount cell population in the field of metabolism-related inflammation; as obesity progresses, a switch takes place within the AT environment from an M2-alternatively activated macrophage state to an M1-inflammatory macrophage-dominated milieu. M1-polarized macrophages secrete inflammatory cytokines like TNF in the obese AT; such cytokines contribute to insulin resistance in adipocytes. Besides macrophages, also CD8+ T cells promote inflammation in the AT and the liver and thereby the deterioration of the metabolic balance in adipocytes and hepatocytes. Other cells of the innate immunity, such as neutrophils or mast cells, interfere with metabolic homeostasis as well. On the other hand, eosinophils or T-regulatory cells, the number of which in the AT decreases in the course of obesity, function to maintain metabolic balance by ameliorating inflammatory processes. In addition, eosinophils and M2-polarized macrophages may contribute to "beige" adipogenesis under lean conditions; beige adipocytes are located predominantly in the subcutaneous AT and have thermogenic and optimal energy-dispensing properties like brown adipocytes. This chapter will summarize the different aspects of the regulation of homeostasis of metabolic tissues by immune cells. |
| DOI: | 10.1007/164_2015_8 |
| 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 |
| 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 |
| S07 | Anti-lipogenesis | de novo lipogenesis; de novo lipogenesis; DNL; anti-lipogenic mechanisms; adipogenesis; anti-obesity | stearoyl-CoA desaturase 1 (SCD-1); Acetyl-coenzyme carboxylase; acyl-CoA carboxylase inhibitor (ACC inhibitor); stearoyl Coenzyme A desaturase inhibitor (SCD inhibitor); THR-beta selective agonist; DGAT2 inhibitor; FASN inhibitor | Aramchol; Firsocostat (GS-0976); VK-2809; ION 224 | 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 | |
|---|---|---|---|---|---|---|---|
| D248 | Obeticholic Acid | Chemical drug | DB05990 | NR1H4 activator; NR1H4 agonist; FXR agonist | Enhance lipid metabolism | Approval rejected | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |