Transcriptomic analysis of Simpson Golabi Behmel syndrome cells during differentiation exhibit BAT-like function

Colitti, Monica; Ali, U.; Wabitsch, Martin; Tews, Daniel

doi:10.1016/j.tice.2022.101822

Cited by 1 publication

(3 citation statements)

References 72 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The lowest down regulated hub genes common to ALLI and cAMP treatments FN1, THBS, COL1A2 and CCN2 were enriched in ECM receptor interactions, integrin cell surface interactions and focal adhesion. This is consistent with the down regulation of collagen, integrin and laminin genes (COL1A1, COL1A2, ITGA2, I T G A 3 , I T G A 4, I T G A5 , L A M A 1 , L A M A 2, L A M A3 ; Supplementary Table 1) observed in SGBS cells during differentiation (20) demonstrating their ability to adjust cytoskeletal reorganization according to their size, LDs dynamics and thermogenesis (71).…”

Section: Discussionsupporting

confidence: 84%

“…Interestingly, all of these genes are downstream targets of the nuclear transcription factor PPARA, which is expressed in metabolically active tissues such as brown adipose tissue (81). In contrast, down regulated DEGs targets of SP1 and other TFs, such as TP53 and JUN, were involved in 'Interleukin-4 and Interleukin-13 signalling' and 'Extracellular matrix organization', 'Cytokine-mediated signalling pathways' and 'IL-18 signalling pathways', as previously described in SGBS cells (20). In particular, the down regulation of fibronectin (FN1), collagen type I alpha 1 chain (COL1A1), collagen type I alpha 2 chain (COL1A2) is associated with that of the zinc finger transcription factor early growth response-1 (EGR1) (Supplementary Table 1) and, in mice, with a concomitant increase of beige cells differentiation and a decrease in genes encoding the extracellular matrix proteins (82).…”

Section: Discussionsupporting

confidence: 55%

“…Previous studies have shown that SGBS cells gradually acquire BAT-like function in the absence of external stimulation during different days of differentiation, suggesting that lipid droplets t dynamics, and mitochondrial morphology (27) together with a differential expression of genes involved in extracellular matrix organization and oxidative stress are related to the brown fat phenotype (20). While it has been clearly demonstrated that the b3-adrenergic receptor (b3-AR) mediates thermogenesis in rodents (54), BAT is activated in humans by b2-AR signalling (55).…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Effects of allicin on human Simpson-Golabi-Behmel syndrome cells in mediating browning phenotype

Ali

Wabitsch²,

Tews³

et al. 2023

Front. Endocrinol.

View full text Add to dashboard Cite

IntroductionObesity is a major health problem because it is associated with increased risk of cardiovascular disease, diabetes, hypertension, and some cancers. Strategies to prevent or reduce obesity focus mainly on the possible effects of natural compounds that can induce a phenotype of browning adipocytes capable of releasing energy in the form of heat. Allicin, a bioactive component of garlic with numerous pharmacological functions, is known to stimulate energy metabolism.MethodsIn the present study, the effects of allicin on human Simpson-Golabi-Behmel Syndrome (SGBS) cells were investigated by quantifying the dynamics of lipid droplets (LDs) and mitochondria, as well as transcriptomic changes after six days of differentiation.ResultsAllicin significantly promoted the reduction in the surface area and size of LDs, leading to the formation of multilocular adipocytes, which was confirmed by the upregulation of genes related to lipolysis. The increase in the number and decrease in the mean aspect ratio of mitochondria in allicin-treated cells indicate a shift in mitochondrial dynamics toward fission. The structural results are confirmed by transcriptomic analysis showing a significant arrangement of gene expression associated with beige adipocytes, in particular increased expression of T-box transcription factor 1 (TBX1), uncoupling protein 1 (UCP1), PPARG coactivator 1 alpha (PPARGC1A), peroxisome proliferator-activated receptor alpha (PPARA), and OXPHOS-related genes. The most promising targets are nuclear genes such as retinoid X receptor alpha (RXRA), retinoid X receptor gamma (RXRG), nuclear receptor subfamily 1 group H member 3 (NR1H3), nuclear receptor subfamily 1 group H member 4 (NR1H4), PPARA, and oestrogen receptor 1 (ESR1).DiscussionTranscriptomic data and the network pharmacology-based approach revealed that genes and potential targets of allicin are involved in ligand-activated transcription factor activity, intracellular receptor signalling, regulation of cold-induced thermogenesis, and positive regulation of lipid metabolism. The present study highlights the potential role of allicin in triggering browning in human SGBS cells by affecting the LD dynamics, mitochondrial morphology, and expression of brown marker genes. Understanding the potential targets through which allicin promotes this effect may reveal the underlying signalling pathways and support these findings.

show abstract

Section: Discussionsupporting

confidence: 84%