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

Abstract

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.

Navigating the landscape of mitochondrial-ER communication in health and disease

“…Proteomic survey studies in human skeletal muscle show decreased levels of SAM50 in obese and diabetic individuals compared to lean subjects ( Hwang et al, 2010 ). Consistently, deletion of SAM50 negatively impacts mitochondrial function brown adipocyte thermogenic functions ( Park et al, 2022 ) which are tightly dependent on ER signaling ( Kato et al, 2020 ; Latorre-Muro et al, 2021 ). These findings connect β-barrel OMM protein insertion with cellular fitness and the onset of metabolic diseases ( Guo et al, 2013 ; Xue et al, 2019 ; Tang et al, 2020 ).…”

PPARγ Protein Expression is Regulated by Cited1 and Cidec in Mouse 3T3-L1 Adipocytes Treated with Troglitazone

“…Furthermore, Cidec has been found to be associated with a lipid droplet protein and thermogenesis. [25][26][27][28] Browning and thermogenesis are metabolic processes that are important for maintaining good health. Cidec and Cited1, which were selected from the apoptotic process term of Gene Ontology in microarray analysis, are representative browning and thermogenesis genes.…”

Paternal developmental thyrotoxicosis disrupts neonatal leptin leading to increased adiposity and altered physiology of the melanocortin system

“…Not surprisingly, the obesity phenotype in EF females was associated with a higher level of serum leptin, and with increased WAT expression of Lep and Mest , two well-established markers of adipose tissue expansion ( 48 – 51 ). Furthermore, EF female WAT also showed reduced expression of Dio2 , an enzyme activated by adrenergic stimuli ( 52 ) and that participates in the “beiging” of adipose tissue ( 53 , 54 ) by locally generating T3 and increasing T3 action ( 55 ). Thus the reduction of Dio2 suggests a lower metabolic level in the WAT of these females.…”