• Journal of Microbiology and Biotechnology
• /
• v.22 no.7
• /
• pp.1029-1033
• /
• 2012

A number of evidence have been accumulated that the regulation of reversible tyrosine phosphorylation, which can be regulated by the combinatorial activity of protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs), plays crucial roles in various biological processes including differentiation. There are a total of 107 PTP genes in the human genome, collectively referred to as the "PTPome." In this study, we performed PTP profiling analysis of the HIB-1B cell line, a brown preadipocyte cell line, during brown adipogenesis. Through RT-PCR and real-time PCR, several PTPs showing differential expression pattern during brown adipogenesis were identified. In the case of PTP-RE, it was shown to decrease significantly until 4 days after brown adipogenic differentiation, followed by a dramatic increase at 6 days. The overexpression of PTP-RE led to decreased brown adipogenic differentiation via reducing the tyrosine phosphorylation of the insulin receptor, indicating that PTP-RE functions as a negative regulator at the early stage of brown adipogenesis.

• BMB Reports
• /
• v.46 no.11
• /
• pp.539-543
• /
• 2013

There is a correlation between obesity and the amount of brown adipose tissue; however, the molecular mechanism of brown adipogenic differentiation has not been as extensively studied. In this study, we performed a protein tyrosine phosphatase (PTP) profiling analysis during the brown adipogenic differentiation of mouse primary brown preadipocytes. Several PTPs, including PTPRF, PTPRZ, and DUSP12 showing differential expression patterns were identified. In the case of DUSP12, the expression level is dramatically downregulated during brown adipogenesis. The ectopic expression of DUSP12 using a retroviral expression system induces the suppression of adipogenic differentiation, whereas a catalytic inactive DUSP12 mutant showed no effect on differentiation. These results suggest that DUSP12 is involved in brown adipogenic differentiation and may be used as a target protein for the treatment or prevention of obesity by the regulation of brown adipogenic differentiation.

• Journal of Microbiology and Biotechnology
• /
• v.29 no.4
• /
• pp.645-650
• /
• 2019

Brown adipocytes have an important role in the regulation of energy balance through uncoupling protein-1 (UCP-1)-mediated nonshivering thermogenesis. Although brown adipocytes have been highlighted as a new therapeutic target for the treatment of metabolic diseases, such as obesity and type II diabetes in adult humans, the molecular mechanism underlying brown adipogenesis is not fully understood. We recently found that protein tyrosine phosphatase receptor type B (PTPRB) expression dramatically decreased during brown adipogenic differentiation. In this study, we investigated the functional roles of PTPRB and its regulatory mechanism during brown adipocyte differentiation. Ectopic expression of PTPRB led to a reduced brown adipocyte differentiation by suppressing the tyrosine phosphorylation of VEGFR2, whereas a catalytic inactive PTPRB mutant showed no effects on differentiation and phosphorylation. Consistently, the expression of brown adipocyte-related genes, such as UCP-1, $PGC-1{\alpha}$, PRDM16, $PPAR-{\gamma}$, and CIDEA, were significantly inhibited by PTPRB overexpression. Overall, these results suggest that PTPRB functions as a negative regulator of brown adipocyte differentiation through its phosphatase activity-dependent mechanism and may be used as a target protein for the regulation of obesity and type II diabetes.

• Journal of Microbiology and Biotechnology
• /
• v.30 no.2
• /
• pp.306-312
• /
• 2020

Despite the importance of brown adipocytes as a therapeutic target for the prevention and treatment of obesity, the molecular mechanism underlying brown adipocyte differentiation is not fully understood. In particular, the role of post-translational modifications in brown adipocyte differentiation has not been extensively studied. Histidine phosphorylation is increasingly recognized an important process for protein post-translational modifications. In this study, we show that histidine phosphorylation patterns change during brown adipocyte differentiation. In addition, the expression level of protein histidine phosphatase 1 (PHPT1), a major mammalian phosphohistidine phosphatase, is reduced rapidly at the early phase of differentiation and recovers at the later phase. During white adipocyte differentiation of 3T3-L1 preadipocytes, however, the expression level of PHPT1 do not significantly change. Knockdown of PHPT1 promotes brown adipocyte differentiation, whereas ectopic expression of PHPT1 suppresses brown adipocyte differentiation. These results collectively suggest that histidine phosphorylation is closely linked to brown adipocyte differentiation and could be a therapeutic target for obesity and related metabolic diseases.

• Molecules and Cells
• /
• v.47 no.2
• /
• pp.100030.1-100030.14
• /
• 2024

Both brown and white adipose tissues (BAT/WAT) are innervated by the peripheral nervous system, including efferent sympathetic nerves that communicate from the brain/central nervous system out to the tissue, and afferent sensory nerves that communicate from the tissue back to the brain and locally release neuropeptides to the tissue upon stimulation. This bidirectional neural communication is important for energy balance and metabolic control, as well as maintaining adipose tissue health through processes like browning (development of metabolically healthy brown adipocytes in WAT), thermogenesis, lipolysis, and adipogenesis. Decades of sensory nerve denervation studies have demonstrated the particular importance of adipose sensory nerves for brown adipose tissue and WAT functions, but far less is known about the tissue's sensory innervation compared to the better-studied sympathetic nerves and their neurotransmitter norepinephrine. In this review, we cover what is known and not yet known about sensory nerve activities in adipose, focusing on their effector neuropeptide actions in the tissue.

• Journal of Marine Life Science
• /
• v.8 no.2
• /
• pp.186-189
• /
• 2023

Uncoupling protein 1 (UCP1) is a unique mitochondrial membranous protein expressed in brown adipose tissue (BAT) in mammals. While its expression in response to cold temperatures and adipogenic inducers is well-characterized in mammals and human infants, the molecular characterization and expression of UCP1 in fish remain unexplored. To address this gap, we analyzed UCP1 expression in response to adipogenic inducers in a fish cell line, rainbow trout gonadal cells (RTG-2), and compared it with UCP1 expression in three mammalian preadipocytes, 3T3-L1, T37i, and WT1 exposed to the Peroxisome proliferator-activated receptor gamma (PPARγ) agonists, rosiglitazone (Rosi). In mammalian preadipocytes, UCP1 protein was highly expressed by Rosi, with an induction of adipogenesis observed in a time-dependent manner. This suggests that UCP1 plays a significant role in adipogenesis in mammals. However, RTG-2 cells showed no response to adipogenic inducers and exhibited only marginal expressions of UCP1. These results imply that RTG-2 cells may lack crucial responsive mechanisms to adipogenic signals or that the adipogenic response is regulated by other mechanisms. Further studies are needed to confirm these phenomena in fish preadipocytes when an appropriate cell line is established in future research.

• Journal of Applied Biological Chemistry
• /
• v.66
• /
• pp.186-196
• /
• 2023

Dyglomera^® is an aqueous ethanol extract derived from the fruit and pods of Dichrostachys glomerata. A previous study has revealed that Dyglomera regulates adipogenesis and lipolysis by modulating AMP-activated protein kinase (AMPK) phosphorylation and increased expression levels of lipolysis-related proteins in white adipose tissue of high fat diet-induced mice and 3T3-L1 adipocyte cells. To further investigate mechanisms of Dyglomera, additional studies were performed using 3T3-L1 cells. Results revealed that Dyglomera downregulated adipogenesis by inhibiting the protein kinase B/mammalian target of rapamycin signaling pathway and reconfirmed that it downregulated gene expression levels of proliferator-activated receptor (PPAR)-γ, CCAAT enhancer binding protein α, sterol-regulation element-binding protein-1c. Dyglomera also reduced adipokines such as tumor necrosis factor alpha, interleukin-1β, and interleukin 6 by regulating leptin expression. Moreover, Dyglomera promoted beige-and-brown adipocyte-related phenotypes and regulated metabolism by increasing mitochondrial number and expression levels of genes such as T-box protein 1, transmembrane protein 26, PR domain 16, and cluster of differentiation 40 as well as thermogenic factors such as uncoupling protein 1, proliferator-activated receptor-gamma co-activator-1α, Sirtuin 1, and PPARα through AMPK activation. Thus, Dyglomera not only can inhibit adipogenesis, but also can promote lipolysis and thermogenesis and regulate metabolism by affecting adipokine secretion from 3T3-L1 adipocytes.

• Journal of Microbiology and Biotechnology
• /
• v.33 no.7
• /
• pp.926-933
• /
• 2023

Aspergillus oryzae KCCM 11372 was used to enhance the production of β-glucan using humidity control strategies. Under conditions of 60% humidity, solid-state fermentation (SSF) increased the yields of enzymes (amylase and protease), fungal biomass (ergosterol), and β-glucan. The maximum concentrations obtained were 14800.58 U/g at 72 h, 1068.14 U/g at 120 h, 1.42 mg/g at 72 h, and 12.0% (w/w) at 72 h, respectively. Moreover, the β-glucan containing fermented brown rice (β-glucan-FBR) extracts at concentrations of 25-300 ㎍/ml was considered noncytotoxic to 3T3-L1 preadipocytes. We then studied the inhibitory effects of the extracts on fat droplet formation in 3T3-L1 cells. As a result, 300 ㎍/ml of β-glucan-FBR extracts showed a high inhibition of 38.88% in lipid accumulation. Further, these extracts inhibited adipogenesis in the 3T3-L1 adipocytes by decreasing the expression of C/EBPα, PPARγ, aP2, and GLUT4 genes.

• Journal of Marine Bioscience and Biotechnology
• /
• v.15 no.2
• /
• pp.59-66
• /
• 2023

Dictyopteris divaricata, a type of marine brown algae, has been studied for its various biological properties, including anti-inflammatory, antidiabetic, and whitening effects. However, its potential antiobesity effects have not been extensively explored. This study aimed to examine the impact of D. divaricata ethanol extract (DDE) on adipocyte differentiation and adipogenesis using 3T3-L1 preadipocytes. Our results showed that when 3T3-L1 preadipocytes were treated with noncytotoxic concentrations of DDE there was a concentration-dependent decrease in fat accumulation rate and triglycerid production compared with the control. Furthermore, DDE significantly reduced the expression of transcription factors (PPARγ, C/EBPα, and SREBP-1) and fatty acid transport protein (FABP4), which are crucial for 3T3-L1 preadipocyte differentiation. These findings suggest that DDE may exhibit antiobesity effects by suppressing the expression of lipogenic transcription factors and fatty acid transport proteins. Therefore, DDE holds potential as a therapeutic agent for obesity.

• Journal of Biomedical Engineering Research
• /
• v.45 no.1
• /
• pp.43-48
• /
• 2024

The prevalence of obesity and its complications is steadily increasing worldwide. It is essential to understand cellular level metabolism and microenvironment to treat diseases related to lipid metabolism. Mechanical loading can activate signaling pathway by stimulating cells, especially vibration loading known to inhibit adipogenesis, so it has been studied as a treatment for obesity. Also, vibration loading can affect the inside of the human body non-invasively. Another clue to reducing adipose tissue is browning, which means that white adipocytes changes to brown adipocyte. In this study, we design and developed a device that that can control cell-cell contact, and vibration simulation device. Using these two devices, we investigated responses of cells to vibration loading. Protein expression associated with browning and adipogenesis were analyzed. In conclusion, vibration loading can be transmitted through cell contact and loading applied to the cells can induce browning and inhibit adipogenesis of preadipocytes. These results suggest the possibility that vibrations could be a treatment for obesity.