ReferenceID 5672
PINK1-PRKN mitophagy suppression by mangiferin promotes a brown-fat-phenotype via PKA-p38 MAPK signalling in murine C3H10T1/2 mesenchymal stem cells
Metabolism
OBJECTIVE: Mangiferin (MF), a xanthonoid derived from Mangifera indica, has shown therapeutic effects on various human diseases including cancer, diabetes, and obesity. Nonetheless, the influence of MF on non-shivering t
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Record Fields
Scalar fields from the final reference record.
- Reference Id
- 5672
- Evidence Id
- 22262
- Core Evidence Id
- 22262
- Source Reference Id
- 4582
- Herb2 Reference Id
- HBREF005379
- Subject Paper Key
- HBIN034394_32289346
- Pubmed Id
- 32289346
- Doi
- 10.1016/j.metabol.2020.154228
- Paper Title
- PINK1-PRKN mitophagy suppression by mangiferin promotes a brown-fat-phenotype via PKA-p38 MAPK signalling in murine C3H10T1/2 mesenchymal stem cells
- Paper Abstract
- OBJECTIVE: Mangiferin (MF), a xanthonoid derived from Mangifera indica, has shown therapeutic effects on various human diseases including cancer, diabetes, and obesity. Nonetheless, the influence of MF on non-shivering thermogenesis and its underlying mechanism in browning remains unclear. Here, our aim was to investigate the effects of MF on browning and its molecular mechanisms in murine C3H10T1/2 mesenchymal stem cells (MSCs). MATERIALS/METHODS: To determine the function of MF on browning, murine C3H10T1/2 MSCs were treated with MF in an adipogenic differentiation cocktail and the thermogenic and correlated metabolic responses were assessed using MF-mediated signalling. Human adipose-derived MSCs were differentiated and treated with MF to confirm its role in thermogenic induction. RESULTS: MF treatment induced the expression of a brown-fat signature, UCP1, and reduced triglyceride (TG) in C3H10T1/2 MSCs. MF also induced the expression of major thermogenesis regulators: PGC1alpha, PRDM16, and PPARgamma and up-regulated the expression of beiging markers CD137, HSPB7, TBX1, and COX2 in both murine C3H10T1/2 MSCs and human adipose-derived mesenchymal stem cells (hADMSC). We also observed that MF treatment increased the mitochondrial DNA and improved mitochondrial homeostasis by regulating mitofission-fusion plasticity via suppressing PINK1-PRKN-mediated mitophagy. Furthermore, MF treatment improved mitochondrial respiratory function by increasing mitochondrial oxygen consumption and expression of oxidative-phosphorylation (OXPHOS)-related proteins. Chemical-inhibition and gene knockdown experiments revealed that beta3-AR-dependent PKA-p38 MAPK-CREB signalling is crucial for MF-mediated brown-fat formation via suppression of mitophagy in C3H10T1/2 MSCs. CONCLUSIONS: MF promotes the brown adipocyte phenotype by suppressing mitophagy, which is regulated by PKA-p38MAPK-CREB signalling in C3H10T1/2 MSCs. Thus, we propose that MF may be a good browning inducer that can ameliorate obesity.
- Journal
- Metabolism
- Publish Year
- 2020
- Experiment Subject
- mouse; human; c3h10t1/2 mscs; human adipose-derived mesenchymal stem cells; human adipose-derived mscs; murine c3h10t1/2 mesenchymal stem cells; murine c3h10t1/2 mscs
- Experiment Type
- Cell Experiment
- Phenotype Related
- Obesity; Diabetes; Cancer
- Paper Title Cn
- Paper Title En
- PINK1-PRKN mitophagy suppression by mangiferin promotes a brown-fat-phenotype via PKA-p38 MAPK signalling in murine C3H10T1/2 mesenchymal stem cells
- Bilingual Status
- semi_complete