Research Article Details
| Article ID: | A52649 |
| PMID: | 24187406 |
| Source: | J Clin Endocrinol Metab |
| Title: | Toll-like receptor status in obesity and metabolic syndrome: a translational perspective. |
| Abstract: | CONTEXT: The prevalence of both obesity and metabolic syndrome (MetS) is increasing at alarming rates globally. Both predispose to diabetes, cardiovascular disease, fatty liver disease, obstructive sleep apnea, and certain cancers. Understanding the mechanisms contributing to increased cardiometabolic risk in obesity and MetS is of utmost importance. EVIDENCE ACQUISITION: For this review, we performed a detailed literature search on PubMed of all publications related to Toll-like receptors (TLRs) and obesity and MetS for the last 20 years. EVIDENCE SYNTHESIS: The TLRs are well-characterized immune receptors that enhance inflammation. The recognition of pathogen-associated molecular patterns and endogenous (host-derived) ligands released by various cell types triggers activation and expression of TLRs. TLRs, especially TLR2 and TLR4, induce insulin resistance, which is pivotal in the pathogenesis of obesity and MetS. Both obesity and MetS are characterized by low-grade chronic inflammation, possibly triggered by activation of TLR2 and TLR4. TLRs, especially TLR4, are activated by fatty acids and endotoxinemia (a marker of gut permeability), features of both obesity and MetS, resulting in activation of nuclear factor-κB and increased release of inflammatory biomediators such as IL-6, IL-1β, TNF-α, and monocyte chemotactic protein-1, which play a role in the pathophysiology of obesity and MetS. Reduction of calories, exercise, and nutraceutical and pharmacological agents can modulate TLRs. CONCLUSIONS: In this review, we present evidence for a pivotal role of TLR-induced inflammation in both obesity and MetS and speculate that targeting these TLRs can forestall their adverse sequelae of diabetes and cardiovascular disease. |
| DOI: | 10.1210/jc.2013-3092 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S08 | Lifestyle measures | Lifestyle intervention; weight loss; diet adaptation; dietary interventions; lifestyle modifications; Exercise | -- | -- | Details |
| 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 | |
|---|---|---|---|---|---|---|---|
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |
| D094 | Cysteamine | Chemical drug | DB00847 | GSS stimulant | Renal drug | Under clinical trials | Details |
| D095 | Cysteamine bitartrate | Chemical drug | DB00847 | -- | -- | Under clinical trials | Details |