Research Article Details
| Article ID: | A48582 |
| PMID: | 33659253 |
| Source: | Front Cell Dev Biol |
| Title: | Polarization of Macrophages in Insects: Opening Gates for Immuno-Metabolic Research. |
| Abstract: | Insulin resistance and cachexia represent severe metabolic syndromes accompanying a variety of human pathological states, from life-threatening cancer and sepsis to chronic inflammatory states, such as obesity and autoimmune disorders. Although the origin of these metabolic syndromes has not been fully comprehended yet, a growing body of evidence indicates their possible interconnection with the acute and chronic activation of an innate immune response. Current progress in insect immuno-metabolic research reveals that the induction of insulin resistance might represent an adaptive mechanism during the acute phase of bacterial infection. In Drosophila, insulin resistance is induced by signaling factors released by bactericidal macrophages as a reflection of their metabolic polarization toward aerobic glycolysis. Such metabolic adaptation enables them to combat the invading pathogens efficiently but also makes them highly nutritionally demanding. Therefore, systemic metabolism has to be adjusted upon macrophage activation to provide them with nutrients and thus support the immune function. That anticipates the involvement of macrophage-derived systemic factors mediating the inter-organ signaling between macrophages and central energy-storing organs. Although it is crucial to coordinate the macrophage cellular metabolism with systemic metabolic changes during the acute phase of bacterial infection, the action of macrophage-derived factors may become maladaptive if chronic or in case of infection by an intracellular pathogen. We hypothesize that insulin resistance evoked by macrophage-derived signaling factors represents an adaptive mechanism for the mobilization of sources and their preferential delivery toward the activated immune system. We consider here the validity of the presented model for mammals and human medicine. The adoption of aerobic glycolysis by bactericidal macrophages as well as the induction of insulin resistance by macrophage-derived factors are conserved between insects and mammals. Chronic insulin resistance is at the base of many human metabolically conditioned diseases such as non-alcoholic steatohepatitis, atherosclerosis, diabetes, and cachexia. Therefore, revealing the original biological relevance of cytokine-induced insulin resistance may help to develop a suitable strategy for treating these frequent diseases. |
| DOI: | 10.3389/fcell.2021.629238 |
| 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 |
| 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 |
| I07 | 1936 | Arteriosclerosis | Build-up of fatty material and calcium deposition in the arterial wall resulting in partial or complete occlusion of the arterial lumen.https://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&ns=ncit&code=C35768 | disease of anatomical entity/cardiovascular system disease/ vascular disease/ artery disease | 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 |
| D579 | Emfilermin | Miscellany | -- | adipocytes | Enhance lipid metabolism | Under investigation | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |