Transcriptome analysis reveals brown adipogenic reprogramming in chemical compound-induced brown adipocytes converted from human dermal fibroblasts

Abstract

Brown adipogenesis contributes to controlling systemic energy balance by enhancing glucose and lipid consumptions. We have previously reported chemical compound-induced brown adipocytes (ciBAs) directly converted from human dermal fibroblasts using a serum-free medium. In this study, genome-wide transcriptional analysis was performed in ciBAs in comparison with the control fibroblasts. A broad range of integrated gene expression was enhanced in functional groups including tricarboxylic acid cycle, electron transfer chain, triglycerides metabolism, fatty acid and glucose metabolism, and adaptive thermogenesis. The results suggested that the chemical conversion underwent metabolic and mitochondrial reprogramming closely associated with functions in brown/beige adipocytes. Moreover, we also compared the transcriptional changes to those of adipocyte browning in adipose tissue-derived mesenchymal stem cells (AdMSCs). Transcriptome analysis indicated that the same sets of metabolic and mitochondria-related genes were similarly changed in the adipocyte browning. Interestingly, ciBAs more expressed Ucp1, while AdMSC-derived adipocytes predominantly expressed Ucp2. UCP1 protein was also more expressed in ciBAs than in AdMSC-derived adipocytes. Based on the evidence that UCP1, but not UCP2, is responsible for adrenergic thermogenesis, ciBAs could be a promising model for human beige adipocytes applicable for basic research, drug development, and clinical uses.

Capsaicin directly promotes adipocyte browning in the chemical compound-induced brown adipocytes converted from human dermal fibroblasts

“…The RNA-Seq analysis revealed that Capsaicin activated not only UCP1 gene but also a series of metabolic genes involved in triglyceride metabolism, fatty acid metabolism, glycolysis pathway, and adaptive thermogenesis. Many of them were overlapped with genes activated during the direct conversion into ciBAs, as shown in our previous analysis 36 , indicating that these metabolic genes are closely associated with functions in brown adipocytes. In addition, this study revealed that Capsaicin activated mitochondrial biogenesis, oxygen consumption, glycolysis, glycerol recycling, and triglyceride accumulation.…”

“…Our previous report suggested that the direct conversion to ciBAs underwent genome-wide transcriptional changes similar to the adipocyte browning in AdMSCs 36 . In contrast, one of the most characteristic differences between them was the expression pattern of major uncoupling proteins.…”

“…Fibroblasts derived from a human subject aged 38 years (HDF38) were mainly used 36 . Approximately 1.5 × 10 5 cells were seeded on a 35-mm dish with high-glucose Dulbecco's Modified Eagle Medium (DMEM) (11995–065, Gibco, MA, USA) supplemented with 10% fetal bovine serum (FBS) (HyClone, UT, USA) and penicillin/streptomycin (Gibco).…”

“…We have previously developed a technique for direct conversion from human dermal fibroblasts into chemical compound-induced brown adipocytes (ciBAs) under serum-containing or serum-free culture conditions 33 – 35 . Furthermore, in a recent study, we have shown that ciBAs undergo a broad range of transcriptional changes that resemble adipocyte browning in adipose tissue-derived mesenchymal stem cells (AdMSCs) 36 . One of the most characteristic differences between them is the expression pattern of major uncoupling proteins.…”

Comprehensive Survey of Using Machine Learning in the COVID-19 Pandemic

“…For example, in [ 180 ], the authors created a dataset of 1933 antigen sequences from similar diseases (SARS, HIV, and EBOLA); then, they trained the XGBoost model (classification model) to predict the antibody that will affect the antigen. Other researchers [ 186 ] tried to predict effective anti-bodies from the future generation of COVID-19. They mutated the SARS antibody sequence and generated 2900 antibody sequences.…”