Thermogenic activation downregulates high mitophagy rate in human masked and mature beige adipocytes
| Autor: | Szatmári-Tóth, Mária, Shaw, Abhirup, Csomós, István, Mocsár, Gábor, Fischer-Posovszky, Pamela, Wabitsch, Martin, Balajthy, Zoltán, Lányi, Cecília, Győry, Ferenc, Kristóf, Endre, Fésüs, László |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
UCP1
Ubiquitin-Protein Ligases Adipocytes White Mitophagy Thermogenesis Cyclic AMP-Dependent Protein Kinases Article Healthy Volunteers lcsh:Chemistry lcsh:Biology (General) lcsh:QD1-999 cAMP LC3 Cyclic AMP Humans beige adipocytes ddc:610 Adipocytes Beige lcsh:QH301-705.5 DDC 610 / Medicine & health Uncoupling Protein 1 Fettzelle Parkin |
| Zdroj: | International Journal of Molecular Sciences, Vol 21, Iss 6640, p 6640 (2020) International Journal of Molecular Sciences Volume 21 Issue 18 |
| DOI: | 10.18725/oparu-47918 |
| Popis: | Thermogenic brown and beige adipocytes oxidize metabolic substrates producing heat, mainly by the mitochondrial uncoupling protein UCP1, and can thus counteract obesity. Masked beige adipocytes possess white adipocyte-like morphology, but can be made thermogenic by adrenergic stimuli. We investigated the regulation of mitophagy upon thermogenic activation of human masked and mature beige adipocytes. Human primary abdominal subcutaneous adipose-derived stromal cells (hASCs) and Simpson&ndash Golabi&ndash Behmel syndrome (SGBS) preadipocytes were differentiated to white and beige adipocytes, then their cAMP-induced thermogenic potential was assessed by detecting increased expressions of UCP1, mitochondrial DNA content and respiratory chain complex subunits. cAMP increased the thermogenic potential of white adipocytes similarly to beige ones, indicating the presence of a masked beige population. In unstimulated conditions, a high autophagic flux and mitophagy rates (demonstrated by LC3 punctae and TOM20 co-immunostaining) were observed in white adipocytes, while these were lower in beige adipocytes. Silencing and gene expression experiments showed that the ongoing mitophagy was Parkin-independent. cAMP treatment led to the downregulation of mitophagy through PKA in both types of adipocytes, resulting in more fragmented mitochondria and increased UCP1 levels. Our data indicates that mitophagy is repressed upon encountering a short-term adrenergic stimulus, as a fast regulatory mechanism to provide high mitochondrial content for thermogenesis. |
| Databáze: | OpenAIRE |
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