• Journal of Life Science
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• v.32 no.4
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• pp.318-324
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• 2022

PPARγ and C/EBPα are master adipogenic transcription factors (TFs) required for adipose tissue development. They control the induction of many adipocyte genes and the early phase of adipogenesis in the embryonic development of adipose tissue. Adipose tissue continues to expand after birth, which, as a late phase of adipogenesis, requires the lipogenesis of adipocytes. In particular, the liver and adipose tissues are major sites for de novo lipogenesis (DNL), where carbohydrates are primarily converted to fatty acids. Furthermore, fatty acids are esterified with glycerol-3-phosphate to produce triglyceride, a major source of lipid droplets in adipocytes. Hepatic DNL has been actively studied, but the DNL of adipocytes in vivo remains not fully understood. Thus, an understanding of lipogenesis and adipose expansion may provide therapeutic opportunities for obesity, type 2 diabetes, and metabolic diseases. In adipocytes, DNL gene expression is transcriptionally regulated by lipogenesis coactivators, as well as by lipogenic TFs such as ChREBP and SREBP1a. Recent in vivo studies have revealed new insights into the lipogenesis gene expression and adipose expansion. Future detailed molecular mechanism studies will determine how nutrients and metabolism regulate DNL and adipose expansion. This review will summarize recent updates of DNL in adipocytes and adipose expansion in terms of transcriptional regulation.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.48 no.4
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• pp.331-342
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• 2022

Obesity is one of the metabolic diseases caused by excessive differentiation and accumulation of adipose tissue due to an imbalance between energy intake and consumption. In this study, we investigated the anti-obesity effect of SliMax, a natural-derived 6 compounds mixture, by using 3T3-L1 cells. As a result, SliMax showed the inhibitory effect on adipocyte differentiation through down-regulation of the PPARγ and C/EBPα expression, which are known to regulate the late adipogenesis stage. In the process of lipolysis on differentiated 3T3-L1 cells, SliMax accelerated decomposition of large-sized unilocular lipid droplet into numerous small-sized multilocular lipid droplets through up-regulation of the expression of lipolysis-related proteins ATGL and HSL. Finally, in order to confirm the effect of SliMax on induction of brown adipocyte, the expression of UCP-1 and the amount of mitochondria were confirmed by immunofluorescent staining, and as a result, SliMax increased the expression of UCP-1 and the amount of mitochondria in fat cells. Taken together, those results suggest that SliMax, a naturally-derived mixture, have a potential to be anti-obesity agent through exerting inhibitory effect on the formation of lipid droplet by suppression of adipogenesis and stimulation of lipolysis, and browning effect associated with generation of heat energy and energy consumption.

• Journal of Physiology & Pathology in Korean Medicine
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• v.28 no.5
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• pp.494-498
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• 2014

It is well known that Desomodii Herba (DH) has an effect to eliminate dampness, relieve jaundice and to clear away toxic material, relieve swelling in Korean Medicine. However, the effect of DH on breast cancer invasion is unknown. In this study, we investigated the inhibitory effect of DH extracts (DHE) on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced matrix metalloproteinase-9 (MMP-9) expression and cell invasion, as well as the molecular mechanisms involved in MCF-7, human breast cancer cells. DHE inhibits TPA-induced MMP-9 protein and mRNA expressions in a dose-dependent fashion. DHE also inhibited the TPA-induced transcriptional activation of nuclear factor-kappa B (NF-${\kappa}B$). These results indicate that DHE-mediated inhibition of TPA-induced MMP-9 expression and cell invasion involves the suppression of NF-${\kappa}B$ pathway in MCF-7 cells.

• Molecules and Cells
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• v.37 no.10
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• pp.734-741
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• 2014

Histone modifications on major transcription factor target genes are one of the major regulatory mechanisms controlling adipogenesis. Plant homeodomain finger 2 (PHF2) is a Jumonji domain-containing protein and is known to demethylate the histone H3K9, a repressive gene marker. To better understand the function of PHF2 in adipocyte differentiation, we constructed stable PHF2 knock-down cells by using the mouse pre-adipocyte cell line 3T3-L1. When induced with adipogenic media, PHF2 knock-down cells showed reduced lipid accumulation compared to control cells. Differential expression using a cDNA microarray revealed significant reduction of metabolic pathway genes in the PHF2 knock-down cell line after differentiation. The reduced expression of major transcription factors and adipokines was confirmed with reverse transcription- quantitative polymerase chain reaction and Western blotting. We further performed co-immunoprecipitation analysis of PHF2 with four major adipogenic transcription factors, and we found that CCATT/enhancer binding protein (C/EBP)${\alpha}$ and C/EBP${\delta}$ physically interact with PHF2. In addition, PHF2 binding to target gene promoters was confirmed with a chromatin immunoprecipitation experiment. Finally, histone H3K9 methylation markers on the PHF2-binding sequences were increased in PHF2 knock-down cells after differentiation. Together, these results demonstrate that PHF2 histone demethylase controls adipogenic gene expression during differentiation.

• The Journal of the Korean Society for Microbiology
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• v.20 no.1
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• pp.55-63
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• 1985

Phosphate, ammonia, glucosamine, glucose, pyruvate, succinate, fumarate, malate and acetate were examined for their ability to control the heat-stable enterotoxin (ST) production in succinate salts medium or in M9 medium. The results obtained were summerized as follows. 1. When the initial phosphate concentration was adjusted to 1.0mM, ST production was decreased to 80u/ml or less. But when the initial phosphate concentration was adjusted to 64mM or 100mM, enterotoxin production was 320u/ml. 2. When the initial ammonia concentration in the medium was adjusted to 1.0mM, no ST production and cell growth were observed. But when ammonia concentration was adjusted to 10mM, 19mM, 38mM or 76mM, enterotoxin production was 320u/ml. 3. Among carbon sources, glucosamine, glucose, pyruvate, succinate, fumarate, malate and acetate, acetate supported the highest specific production (928 unit/O.D.) of heat-stable enterotoxin. From this results, we could assume that heat-stable enterotoxin production is controlled by stringent control mechanism. 4. When the pH of the succinate salts medium was kept between 6.2 to 6.5, no heat-stable enterotoxin production was observed, but when the pH of the medium was kept between pH 6.2 to 6.5, 267 unit/O.D. of heat-stable enterotoxin was produced. 5. Glucose inhibited the heat-stable enterotoxin production and the mechanism was assumed due to its capacity to lower the pH of the medium during catabolysis and its high metabolic energy.

• The Korean Journal of Physiology
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• v.30 no.2
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• pp.231-236
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• 1996

In our previous study (Kim et al, 1991), GLUT 4 protein content correlated negatively with plasma glucose levels in skeletal muscles of STZ-induced diabetic rats. Thus, in this study, to confirm whether expression of GLUT 4 correlate negatively with degree of hyperglycemia, we measured levels of GLUT 4 mRNA in red and white gastrocnemius muscles in STZ-induced mild and severe diabetic rats. Rats were randomly assigned to control, mild, and severe diabetic groups, and the diabetes was induced by intraperitoneal administration of STZ. The experiment was carried out 10 days after STZ administration. Gastrocnemius red and white muscles were used fur the measurement of GLUT 4 expression. Plasma glucose levels of mild and severe diabetic rats were increased compared to control rats (control, mild, and severe diabetes; $6.4{\pm}0.32,\;9.4{\pm}0.68,\;and\;22.0{\pm}0.58$ mmol/L, respectively). Plasma insulin levels of mild and severe diabetic rats were decreased compared to control rats (control, mild, and severe diabetes; $198{\pm}37,\;l14{\pm}14,\;and\;90{\pm}15$ pmol/L, respectively). GLUT 4 mRNA levels of gastrocnemius red muscles in mild and severe diabetic rats were decreased compared to control rats ($64{\pm}1.2%\;and\;71{\pm}2.0%$ of control, respectively), but GLUT 4 mRNA levels in gastrocnemius white muscles were unaltered in diabetic rats. In summary, GLUT 4 mRNA levels were decreased in STZ-induced diabetic rats but did not correlated negatively with degree of hyperglycemia, and this result suggest that the regulatory mechanisms of decreased GLUT 4 mRNA levels are hypoinsulinemia and/or other metabolic factor but not hyperglycemia. And regulation of GLUT 4 expression in STZ-induced diabetes between red and white enriched skeletal muscles may be related to a fiber specific gene regulatory mechanism.

• Journal of Sasang Constitutional Medicine
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• v.24 no.4
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• pp.75-83
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• 2012

Objectives : Although Yeoldahanso-tang (YDHST) has been widely used for treatment of obesity and its related diseases such as hyperinsulinemia and hypertension for Taeeumin, no scientific evidence has reported yet to support its ability to work against these metabolic disorders. Our study was aimed to investigate the anti-obesity effect of YDHST extract on the cellular differentiation of 3T3-L1 preadipocytes into adipocytes. Methods : 3T3-L1 preadipocytes were differentiated into adipocytes by adding insulin, dexamethasone and 3-isobutyl-1-methylxanthine (IBMX) for 8 days in the absence or presence of YDHST extract. Anti-obesity effects of YDHST extract were evaluated by Oil Red O staining, glycerol-3-phosphate dehydrogenase (GPDH) activity, triglyceride contents, and leptin production. Results : YDHST extract remarkably prevented lipid accumulation with no cytotoxicity in the differentiated 3T3-L1 cells. In addition, YDHST extract decreased contents of triglyceride 3T3-L1 adipocytes. Consistently, YDHST extract caused a significant inhibition of GPDH activity and leptin production in a dose-dependent manner. Conclusions : Our findings suggest that Sasang constitutional herbal formula YDHST for Tae-eumin has anti-obesity activity by regulation of the adipogenesis process in vitro. Additional study will be required to further confirm the inhibitory effect on adipocyte differentiation by using in vivo animal model.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.10
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• pp.4655-4659
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• 2016

Background and Aim: Breast cancer is a major healthcare problem in women. There are many reports about up-regulation of Hsp27 in cancer tissues but less is known about the potential relationship between Hsp27 antibody levels and breast cancer complications. We here investigated concentrations of serum Hsp27 antigen and antibodies in subjects with and without breast cancer and assessed potential associations with two-year disease-free survival, histological grade and number of lymph nodes. Materials and Methods: Specifically, serum Hsp27 antigen and antibody levels from 97 patients with breast cancer, and 65 healthy controls were determined by enzyme-linkedimmunosorbent assays (ELISAs). Results: Serum Hsp27 and antibody levels were significantly (p<0.001) higher in patients with breast cancer compared to the control group, but no relationship were found with two-year disease free survival, histological grade or number of lymph nodes (p> 0.6, 0.2 and 0.9 respectively). Conclusions: Elevated levels of Hsp27 antibody occur with women with breast cancer but do not appear to be associated with the presence of disease clinical complications.

• Development and Reproduction
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• v.16 no.4
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• pp.253-264
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• 2012

Nesfatin-1 is a recently discovered anorexigenic peptide which is distributed in several brain areas implicated in the feeding and metabolic regulation. Recently, it has been reported that nesfatin-1 is expressed not only in brain, but also in peripheral organs such as digestive organs, adipose tissues, heart, and reproductive organs. Nesfatin-1 is markedly expressed in the pancreas, stomach and duodenum. Eventually, the nesfatin-1 expression in the digestive organs may be regulated by nutritional status, which suggests a regulatory role of peripheral nesfatin-1 in energy homeostasis. Nesfatin-1 is also detected in the adipose tissues of humans and rodents, indicating that nesfatin-1 expression in the fat may regulate food intake independently, rather than relying on leptin. In addition, nesfatin-1 is expressed in the heart as a cardiac peptide. It suggests that nesfatin-1 may regulate cardiac function and encourage clinical potential in the presence of nutrition-dependent physio-pathologic cardiovascular diseases. Currently, only a few studies demonstrate that nesfatin-1 is expressed in the reproductive system. However, it is not clear yet what function of nesfatin-1 is in the reproductive organs. Here, we summarize the expression of nesfatin-1 and its roles in brain and peripheral organs and discuss the possible roles of nesfatin-1 expressed in reproductive organs, including testis, epididymis, ovary, and uterus. We come to the conclusion that nesfatin-1 as a local regulator in male and female reproductive organs may regulate the steroidogenesis in the testis and ovary and the physiological activity in epididymis and uterus.

• Molecules and Cells
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• v.27 no.6
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• pp.641-649
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• 2009

Pyrophosphate:fructose-6-phosphate 1-phosphotransferase (PFP) catalyzes the reversible interconversion of fructose-6-phosphate and fructose-1,6-bisphosphate, a key step in the regulation of the metabolic flux toward glycolysis or gluconeogenesis. To examine the role of PFP in plant growth, we have generated transgenic Arabidopsis plants that either overexpress or repress Arabidopsis PFP subunit genes. The overexpressing lines displayed increased PFP activity and slightly faster growth relative to wild type plants, although their photosynthetic activities and the levels of metabolites appeared not to have significantly changed. In contrast, the RNAi lines showed significantly retarded growth in parallel with the reduced PFP activity. Analysis of photosynthetic activity revealed that the growth retardation phenotype of the RNAi lines was accompanied by the reduced rates of $CO_2$ assimilation. Microarray analysis of our transgenic plants further revealed that the altered expression of $AtPFP{\beta}$ affects the expression of several genes involved in diverse physiological processes. Our current data thus suggest that PFP is important in carbohydrate metabolism and other cellular processes.