• 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 Life Science
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• v.24 no.5
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• pp.573-587
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• 2014

Angiogenesis, the formation of new capillary blood vessels, is a tightly regulated process. Under normal physiological conditions, angiogenesis only takes place during embryonic development, wound healing, and female menstruation. Dysregulation of angiogenesis is associated with many diseases, such as cancer, rheumatoid arthritis, psoriasis, and proliferative retinopathy. The growth and expansion of adipose tissue require the formation of new blood vessels. Adipose tissue is probably the most highly vascularized tissue in the body, as each adipocyte is surrounded by capillaries, and the angiogenic vessels supply nutrients and oxygen to adipocytes. Accumulating evidence shows that capillary endothelial cells communicate with adipocytes via paracrine signaling pathways, extracellular components, and direct cell-cell interactions. Activated adipocytes produce multiple angiogenic factors, including VEGF, FGF-2, leptin, and HGF, which either alone or cooperatively stimulate the expansion and metabolism of adipose tissue by increasing adipose tissue vasculature. Recently, it was demonstrated that antiangiogenic herbal Ob-X extracts and Korean red ginseng extracts reduce adipose tissue mass and suppress obesity by inhibiting angiogenesis in obese mice. Thus, angiogenesis inhibitors provide a promising therapeutic approach for controlling human obesity and related disorders.

• Archives of Plastic Surgery
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• v.39 no.6
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• pp.585-592
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• 2012

During the past decade, many studies using platelet-rich plasma (PRP) or adipose-derived stem cells (ASCs) have been conducted in various medical fields, from cardiovascular research to applications for corneal diseases. Nonetheless, there are several limitations of practical applications of PRP and ASCs. Most reports of PRP are anecdotal and few include controls to determine the specific role of PRP. There is little consensus regarding PRP production and characterization. Some have reported the development of an antibody to bovine thrombin, which was the initiator of platelet activation. In the case of ASCs, good manufacturing practices are needed for the production of clinical-grade human stem cells, and in vitro expansion of ASCs requires approval of the Korea Food and Drug Administration, such that considerable expense and time are required. Additionally, some have reported that ASCs could have a potential risk of transformation to malignant cells. Therefore, the authors tried to investigate the latest research on the efficacy and safety of PRP and ASCs and report on the current state and regulation of these stem cell-based therapies.

• Archives of Plastic Surgery
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• v.43 no.5
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• pp.466-469
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• 2016

External volume expansion of the recipient site by suction has been proposed as a way of improving fat graft survival. The objective of this study was to present an innovative and simple intraoperative external expansion system to enhance small-volume autologous fat grafting (40-80 mL) and to discuss its background and its mechanism of action. In this system, expansion is performed using a complete vacuum delivery system known as the Kiwi VAC-6000M with a PalmPump (Clinical Innovations). The recipient site is rapidly expanded intraoperatively 10 times for 30 seconds each with a negative pressure of up to 550 mm Hg before autologous fat injection. During this repetitive stimulation, the tissues become grossly expanded, developing macroscopic swelling that regresses slowly over the course of hours following the cessation of the stimulus. The system sets various mechanisms in motion, including scar release, mechanical stimulation, edema, ischemia, and inflammation, which provide an environment conducive for cell proliferation and angiogenesis. In order to maintain the graft construct in its expansive state, all patients are encouraged postoperatively to use the Kiwi three times daily for one minute per session over the course of three days. The handling of this system is simple for both the patients and the surgeon. Satisfactory clinical outcomes have been achieved without significant complications.

• Journal of Life Science
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• v.17 no.5 s.85
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• pp.678-686
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• 2007

Human mesenchymal stem cells(hMSC), that have been reported to be present in bone marrow, adipose tissues, dermis, muscles and peripheral blood, have the potential to differentiate along different lineages including those forming bone, cartilage, fat, muscle and neuron. Therefore, hMSC are attractive candidates for cell and gene therapy. The optimal conditions for hMSC expansion require medium supplemented with fetal bovine serum(FBS). Some forms of cell therapy will involve multiple doses, raising a concern over immunological reactions caused by medium-derived FBS proteins. Previously, we have shown that hADSC can be cultured in human serum(HS) during their isolation and expansion, and that they maintain their proliferative capacity and ability for multilineage differentiation and promote engraftment of peripheral blood-derived CD34 cells mobilized from bone marrow in NOD/SCID mice. In this study we determined whether hADSC grown in HS maintain surface markers expression similar with cells grown in FBS during culture expansion and compared gene expression profile by Affymetrix microarray. Flow cytometry analysis showed that HLA-DR, CD117, CD29 and CD44 expression in HS-cultured hADSC during culture expansion were similar with that in FBS-cultured cells. However, the gene expression profile in HS-cultured hADSC was significantly different from that in FBS-cultured cells. Therefore, these data indicated that HS-cultured hADSC should be used in vivo animal study of hADSC transplantation for direct extrapolation of preclinical data into clinical application.

• BMB Reports
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• v.50 no.11
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• pp.572-577
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• 2017

In most clinical applications, human mesenchymal stem cells (hMSCs) are expanded in large scale before their administration. Prolonged culture in vitro results in cellular senescence-associated phenotypes, including accumulation of reactive oxygen species (ROS) and decreased cell viabilities. Profiling of stem cell-related genes during in vitro expansion revealed that numerous canonical pathways were significantly changed. To determine the effect of selenocysteine (Sec), a rare amino acid found in several antioxidant enzymes, on the replicative senescence in hMSCs, we treated senescent hMSCs with Sec. Supplementation of Sec in the culture medium in late-passage hMSCs reduced ROS levels and improved the survival of hMSCs. In addition, a subset of key antioxidant genes and Sec-containing selenoproteins showed increased mRNA levels after Sec treatment. Furthermore, ROS metabolism and inflammation pathways were predicted to be downregulated. Taken together, our results suggest that Sec has antioxidant effects on the replicative senescence of hMSCs.

• Development and Reproduction
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• v.23 no.3
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• pp.213-221
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• 2019

The epididymal fat of mouse is a part of visceral fat deposit and is divided into the distal or proximal part based on its histochemical characteristics. Even though the formation of the epididymal fat pad begins before the birth, a detailed adipogenic procedure of the epididymal fat has not been revealed. The epididymal fat pad becomes enlarged and expended with age, and expressional changes of numerous genes are associated with the maturation of fat tissues. In the present research, expressional patterns of adipose tissue-related genes in the distal epididymal fat of mouse at 2, 5, 8, and 12 months of postnatal age were determined by a quantitative real-time polymerase chain reaction (PCR) analysis. The lowest transcript levels of fatty acid binding protein 4 (Fabp4), lipoprotein lipase (Lpl), delta like non-canonical Notch ligand 1 (Dlk1), peroxisome proliferator-activated receptor gamma (Pparg), leptin (Lep), adiponectin (Adipoq), and resistin (Retn) were detected at 2 months of age, except fatty acid synthase (Fasn) showing the lowest level at 5 months of age. Even though expression of Lep and Fabp4 were gradually increased until 12 months of age, significant increases of Pparg and Adipoq transcript levels were continued until 8 months of age. The transcript levels of Lpl, Rent, Dlk1, and Fasn were significantly increased at 8 months of age, compared with those at 2 months of age. The current findings suggest that the expansion of the distal epididymal fat of mouse during postnatal period would be companied with differential expression of various adipocyte-associated molecules.

• BMB Reports
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• v.52 no.3
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• pp.220-225
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• 2019

We have identified a mechanism to diminish the proliferative capacity of cells during cell expansion using human adipose-derived stromal cells (hAD-SCs) as a model of replicative senescence. hAD-SCs of high-passage numbers exhibited a reduced proliferative capacity with accelerated cellular senescence. Levels of key bioactive sphingolipids were significantly increased in these senescent hAD-SCs. Notably, the transcription of sphingosine kinase 1 (SPHK1) was down-regulated in hAD-SCs at high-passage numbers. SPHK1 knockdown as well as inhibition of its enzymatic activity impeded the proliferation of hAD-SCs, with concomitant induction of cellular senescence and accumulation of sphingolipids, as seen in high-passage cells. SPHK1 knockdown-accelerated cellular senescence was attenuated by co-treatment with sphingosine-1-phosphate and an inhibitor of ceramide synthesis, fumonisin $B_1$, but not by treatment with either one alone. Together, these results suggest that transcriptional down-regulation of SPHK1 is a critical inducer of altered sphingolipid profiles and enhances replicative senescence during multiple rounds of cell division.

• Korean Journal of Radiology
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• v.24 no.10
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• pp.974-982
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• 2023

Objective: Recent studies have highlighted the active and potential role of perivascular adipose tissue (PVAT) in atherosclerosis and aneurysm progression, respectively. This study explored the link between PVAT attenuation and abdominal aortic aneurysm (AAA) progression using computed tomography angiography (CTA). Materials and Methods: This multicenter retrospective study analyzed patients with AAA who underwent CTA at baseline and follow-up between March 2015 and July 2022. The following parameters were obtained: maximum diameter and total volume of the AAA, presence or absence of intraluminal thrombus (ILT), maximum diameter and volume of the ILT, and PVAT attenuation of the aortic aneurysm at baseline CTA. PVAT attenuation was divided into high (> -73.4 Hounsfield units [HU]) and low (≤ -73.4 HU). Patients who had or did not have AAA progression during the follow-up, defined as an increase in the aneurysm volume > 10 mL from baseline, were identified. Kaplan-Meier and multivariable Cox regression analyses were used to investigate the association between PVAT attenuation and AAA progression. Results: Our study included 167 participants (148 males; median age: 70.0 years; interquartile range: 63.0-76.0 years), of which 145 (86.8%) were diagnosed with AAA accompanied by ILT. Over a median period of 11.3 months (range: 6.0-85.0 months), AAA progression was observed in 67 patients (40.1%). Multivariable Cox regression analysis indicated that high baseline PVAT attenuation (adjusted hazard ratio [aHR] = 2.23; 95% confidence interval [CI], 1.16-4.32; P = 0.017) was independently associated with AAA progression. This association was demonstrated within the patients of AAA with ILT subcohort, where a high baseline PVAT attenuation (aHR = 2.23; 95% CI, 1.08-4.60; P = 0.030) was consistently independently associated with AAA progression. Conclusion: Elevated PVAT attenuation is independently associated with AAA progression, including patients of AAA with ILT, suggesting the potential of PVAT attenuation as a predictive imaging marker for AAA expansion.

• Asian-Australasian Journal of Animal Sciences
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• v.30 no.1
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• pp.111-118
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• 2017

Objective: Adipose tissue plays a key role in the development of obesity and diabetes. We previously reported that lignosulfonic acid suppresses the rise in blood glucose levels through the inhibition of ${\alpha}$-glucosidase activity and intestinal glucose absorption. The purpose of this study is to examine further biological activities of lignosulfonic acid. Methods: In this study, we examined the effect of lignosulfonic acid on differentiation of 3T3-L1 cells. Results: While lignosulfonic acid inhibited proliferation (mitotic clonal expansion) after induction of differentiation, lignosulfonic acid significantly increased the size of accumulated lipid droplets in the cells. Semi-quantitative reverse transcription polymerase chain reaction analysis showed that lignosulfonic acid increased the expression of the adipogenic transcription factor, peroxisome proliferator-activated receptor gamma ($PPAR{\gamma}$), leading to increased glucose transporter 4 (Glut-4) expression and 2-deoxyglucose uptake in differentiated 3T3-L1 cells. Additionally, feeding lignosulfonic acid to diabetic KK-Ay mice suppressed increase of blood glucose level. Conclusion: Lignosulfonic acid may be useful as a functional anti-diabetic component of food.