Research Article Details
| Article ID: | A48639 |
| PMID: | 32592089 |
| Source: | J Physiol Biochem |
| Title: | Lactosylceramide induced by elastin-derived peptides decreases adipocyte differentiation. |
| Abstract: | Elastin, the major protein of the extracellular matrix, is specially found in cardiovascular tissues and contributing to 30-50% of the dry weight of blood vessels. Elastin regulates cell signalling pathways involved in morphogenesis, injury response and inflammation. The function of elastin is frequently compromised in damaged or aged elastic tissues. Indeed, elastin degradation, observed during ageing, and the resulting production of elastin-derived peptides (EDPs), have crucial impacts on cardiovascular disease (atherosclerosis, thrombosis) or on metabolism disease progressions (type 2 diabetes or non-alcoholic steatohepatitis). In the present study, we analysed the EDP effects on 3T3 preadipocyte cell differentiation. In a first part, we treated 3T3-L1 cells with EDP and visualized the lipid droplet accumulation by the oil red O staining and measured the expression of various transcription factors and adipocyte-specific mRNAs by real-time RT-PCR. We demonstrated that the elastin receptor complex, ERC, is activated by EDPs and decreased adipocyte differentiation by a modulation of crucial adipogenesis transcriptional factor particularly PPARγ. In a second part, we identified the signalling pathway implicated in EDP-reduced cell differentiation. The flow cytometry and immunocytochemistry approaches showed that ERC activated by EDP produced a second messenger, lactosylceramide (Lac-Cer). Moreover, this Lac-Cer production favoured the phosphorylation of ERK1-2 (p-ERK1-2), to decrease adipocyte differentiation by a modulation of adipogenesis transcriptional factor PPARγ. To conclude, the EDP/Lac-Cer/p-ERK1-2 signalling pathway may be studied further as a critical target for treating complications associated with adipocyte dedifferentiation such as obesity and diabetes insulin resistance. |
| DOI: | 10.1007/s13105-020-00755-z |
| 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 |
| 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 |
| 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 |
| 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 |