SAMM50 Regulates Thermogenesis of Beige Adipocytes Differentiated from Human Adipose-Derived Stem Cells by Balancing Mitochondrial Dynamics.

Brown/beige adipocyte thermogenesis is a process that is important for energy balance. The thermogenesis of brown/beige adipocytes occurs in the mitochondria, which is modulated by the dynamic balance between mitochondrial fusion and fission. Mitophagy is also involved in mitochondrial dynamics. The sorting and assembly machinery (SAM) complex protein, SAMM50, plays a key role in mitochondrial dynamics and quality control through regulating mitophagy. However, the roles of SAMM50 in the thermogenesis of beige adipocytes remain unknown. Thus, the objective of this study was to conduct functional analyses of SAMM50. The expression of mitochondrial fusion genes was repressed by SAMM50 knockdown but was not altered by SAMM50 overexpression. These results agreed with the distribution of the fluorescence-stained mitochondria and an mtDNA copy number. In contrast, the expression of mitochondrial fission genes showed an opposite outcome. As a result, suppression by the SAMM50 shRNA inhibited the expression of thermogenic genes (UCP1, PPARGC1A, DIO2, ELOVL3, CIDEA, and CIDEC) and mitochondrial-related genes (CYCS, COX7A1, TFAM, CPT1B, and CPT2). Conversely, SAMM50 overexpression promoted the expression of the thermogenic genes and mitochondrial genes. Thus, SAMM50 links the balance between the mitochondrial dynamics and thermogenesis of beige adipocytes.

Extract of Ephedra sinica Stapf Induces Browning of Mouse and Human White Adipocytes.

Browning of adipocytes using herbal extracts is an attractive and realistic strategy for obesity treatment. Ephedra sinica Stapf (E. sinica) is an Asian traditional medicine known to activate brown adipocytes. To evaluate the effect of E. sinica (EEs) on the browning of white adipocytes, expression levels of browning markers, including uncoupling protein 1 (UCP1), were determined using qPCR, Western blot, and immunocytochemistry after mature mouse inguinal preadipocyte (mIPA) and human adipose-derived stem cells (hADSCs) were treated with EEs. In addition, mitochondrial activity was determined by analyzing MitoTracker staining, mtDNA copy number, and oxygen consumption rate (OCR). Treatment with EEs suppressed lipid accumulation and expression levels of adipogenic markers, including Pparg, during mIPA differentiation. In mature mIPA and hADSCs browning markers, including Ucp1, were up-regulated by EEs. In addition, EEs increased expression of mitochondrial genes, mtDNA copy number, and OCR. EEs showed a dual function: inhibiting adipogenesis in immature preadipocytes, and promoting thermogenesis via browning in mature white adipocytes. Therefore, E. sinica is a potential herb for regulating energy metabolism by inducing the browning process.