Research Article Details
| Article ID: | A26025 |
| PMID: | 22566839 |
| Source: | Front Immunol |
| Title: | New insights into the role of macrophages in adipose tissue inflammation and Fatty liver disease: modulation by endogenous omega-3 Fatty Acid-derived lipid mediators. |
| Abstract: | Obesity is causally linked to a chronic state of "low-grade" inflammation in adipose tissue. Prolonged, unremitting inflammation in this tissue has a direct impact on insulin-sensitive tissues (i.e., liver) and its timely resolution is a critical step toward reducing the prevalence of related co-morbidities such as insulin resistance and non-alcoholic fatty liver disease. This article describes the current state-of-the-art knowledge and novel insights into the role of macrophages in adipose tissue inflammation, with special emphasis on the progressive changes in macrophage polarization observed over the course of obesity. In addition, this article extends the discussion to the contribution of Kupffer cells, the liver resident macrophages, to metabolic liver disease. Special attention is given to the modulation of macrophage responses by omega-3-PUFAs, and more importantly by resolvins, which are potent anti-inflammatory and pro-resolving autacoids generated from docosahexaenoic and eicosapentaenoic acids. In fact, resolvins have been shown to work as endogenous "stop signals" in inflamed adipose tissue and to return this tissue to homeostasis by inducing a phenotypic switch in macrophage polarization toward a pro-resolving phenotype. Collectively, this article offers new views on the role of macrophages in metabolic disease and their modulation by endogenously generated omega-3-PUFA-derived lipid mediators. |
| DOI: | 10.3389/fimmu.2011.00049 |
| 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 |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D258 | Omega 3 PUFA | Chemical drug | DB11133 | PPARG ligand; PPARA activator | Hypolipidemic drug | Under clinical trials | Details |
| D328 | Serine | Chemical drug | DB00133 | SRR | Improve insulin resistance | Under clinical trials | Details |
| D105 | DHA | Chemical drug | DB03756 | PPARA ligand; PPARG ligand | Anti-inflammatory | Under clinical trials | Details |
| D527 | EPA/DHA | Supplement | DB11133 | -- | -- | Under clinical trials | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |
| D504 | Polyunsaturated Fatty Acids | Supplement | -- | -- | -- | Under clinical trials | Details |
| D125 | Epanova | Chemical drug | DB11133 | PPARG ligand; PPARA activator | Enhance lipid metabolism | Under clinical trials | Details |