Research Article Details
| Article ID: | A03639 |
| PMID: | 33923175 |
| Source: | Cells |
| Title: | Adipocyte, Immune Cells, and miRNA Crosstalk: A Novel Regulator of Metabolic Dysfunction and Obesity. |
| Abstract: | Obesity is characterized as a complex and multifactorial excess accretion of adipose tissue (AT) accompanied with alterations in the immune response that affects virtually all age and socioeconomic groups around the globe. The abnormal accumulation of AT leads to several metabolic diseases, including nonalcoholic fatty liver disorder (NAFLD), low-grade inflammation, type 2 diabetes mellitus (T2DM), cardiovascular disorders (CVDs), and cancer. AT is an endocrine organ composed of adipocytes and immune cells, including B-Cells, T-cells and macrophages. These immune cells secrete various cytokines and chemokines and crosstalk with adipokines to maintain metabolic homeostasis and low-grade chronic inflammation. A novel form of adipokines, microRNA (miRs), is expressed in many developing peripheral tissues, including ATs, T-cells, and macrophages, and modulates the immune response. miRs are essential for insulin resistance, maintaining the tumor microenvironment, and obesity-associated inflammation (OAI). The abnormal regulation of AT, T-cells, and macrophage miRs may change the function of different organs including the pancreas, heart, liver, and skeletal muscle. Since obesity and inflammation are closely associated, the dysregulated expression of miRs in inflammatory adipocytes, T-cells, and macrophages suggest the importance of miRs in OAI. Therefore, in this review article, we have elaborated the role of miRs as epigenetic regulators affecting adipocyte differentiation, immune response, AT browning, adipogenesis, lipid metabolism, insulin resistance (IR), glucose homeostasis, obesity, and metabolic disorders. Further, we will discuss a set of altered miRs as novel biomarkers for metabolic disease progression and therapeutic targets for obesity. |
| DOI: | 10.3390/cells10051004 |
| 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 |
| S02 | Enhance lipid metabolism | triglyceride-lowering; lipid tolerance; lipid metabolism | 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) inhibitor; Decreases intestinal cholesterol absorption; FXR agonist; ACC inhibitor; FAS inhibitor; DGAT2 inhibitor; SCD-1 inhibitor | Atorvastatin; Ezetimibe; Obeticholic Acid; GS-9674; GS-0976; TVB-2640; IONIS-DGAT2rx; Aramchol; | 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 |