Publications by authors named "Jae-Bum Kim"

159 Publications

DNMT1 maintains metabolic fitness of adipocytes through acting as an epigenetic safeguard of mitochondrial dynamics.

Proc Natl Acad Sci U S A 2021 Mar;118(11)

National Creative Research Initiatives Center for Adipocyte Structure and Function, Seoul National University, Seoul 08826, South Korea;

White adipose tissue (WAT) is a key regulator of systemic energy metabolism, and impaired WAT plasticity characterized by enlargement of preexisting adipocytes associates with WAT dysfunction, obesity, and metabolic complications. However, the mechanisms that retain proper adipose tissue plasticity required for metabolic fitness are unclear. Here, we comprehensively showed that adipocyte-specific DNA methylation, manifested in enhancers and CTCF sites, directs distal enhancer-mediated transcriptomic features required to conserve metabolic functions of white adipocytes. Particularly, genetic ablation of adipocyte Dnmt1, the major methylation writer, led to increased adiposity characterized by increased adipocyte hypertrophy along with reduced expansion of adipocyte precursors (APs). These effects of Dnmt1 deficiency provoked systemic hyperlipidemia and impaired energy metabolism both in lean and obese mice. Mechanistically, Dnmt1 deficiency abrogated mitochondrial bioenergetics by inhibiting mitochondrial fission and promoted aberrant lipid metabolism in adipocytes, rendering adipocyte hypertrophy and WAT dysfunction. Dnmt1-dependent DNA methylation prevented aberrant CTCF binding and, in turn, sustained the proper chromosome architecture to permit interactions between enhancer and dynamin-1-like protein gene (Drp1) in adipocytes. Also, adipose DNMT1 expression inversely correlated with adiposity and markers of metabolic health but positively correlated with AP-specific markers in obese human subjects. Thus, these findings support strategies utilizing Dnmt1 action on mitochondrial bioenergetics in adipocytes to combat obesity and related metabolic pathology.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1073/pnas.2021073118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7980432PMC
March 2021

Extracorporeal Membrane Oxygenation for Coronavirus Disease 2019: Expert Recommendations from The Korean Society for Thoracic and Cardiovascular Surgery.

J Chest Surg 2021 Feb;54(1):2-8

Department of Thoracic and Cardiovascular Surgery, Pusan National University Hospital, Pusan National University School of Medicine, Busan, Korea.

Since the first reported case of coronavirus disease 2019 (COVID-19) in December 2019, the numbers of confirmed cases and deaths have continued to increase exponentially despite multi-factorial efforts. Although various attempts have been made to improve the level of evidence for extracorporeal membrane oxygenation (ECMO) treatment over the past 10 years, most experts still hesitate to take an active position on whether to apply ECMO in COVID-19 patients. Several ECMO management guidelines have been published recently, but they reflect some important differences from the Korean medical system and aspects of real-world medical practice in Korea. We aimed to find evidence on the efficacy of ECMO for COVID-19 patients by reviewing the published literature and to propose expert recommendations by analyzing the Korean COVID-19 ECMO registry data.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5090/kjtcs.21.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7946520PMC
February 2021

Adipocytes Are the Control Tower That Manages Adipose Tissue Immunity by Regulating Lipid Metabolism.

Front Immunol 2020 28;11:598566. Epub 2021 Jan 28.

National Creative Research Initiatives Center for Adipocyte Structure and Function, Seoul National University, Seoul, South Korea.

Accumulating evidence reveals that adipose tissue is an immunologically active organ that exerts multiple impacts on the regulation of systemic energy metabolism. Adipose tissue immunity is modulated by the interactions between adipocytes and various immune cells. Nevertheless, the underlying mechanisms that control inter-cellular interactions between adipocytes and immune cells in adipose tissue have not been thoroughly elucidated. Recently, it has been demonstrated that adipocytes utilize lipid metabolites as a key mediator to initiate and mediate diverse adipose tissue immune responses. Adipocytes present lipid antigens and secrete lipid metabolites to determine adipose immune tones. In addition, the interactions between adipocytes and adipose immune cells are engaged in the control of adipocyte fate and functions upon metabolic stimuli. In this review, we discuss an integrated view of how adipocytes communicate with adipose immune cells using lipid metabolites. Also, we briefly discuss the newly discovered roles of adipose stem cells in the regulation of adipose tissue immunity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2020.598566DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876236PMC
January 2021

Phenotypic Discovery of SB1501, an Anti-obesity Agent, through Modulating Mitochondrial Activity.

ChemMedChem 2021 Apr 10;16(7):1104-1115. Epub 2021 Mar 10.

CRI Center for Chemical Proteomics, Department of Chemistry, Seoul National University, Seoul, 08826, Korea.

Obesity has become a pandemic that threatens the quality of life and discovering novel therapeutic agents that can reverse obesity and obesity-related metabolic disorders are necessary. Here, we aimed to identify new anti-obesity agents using a phenotype-based approach. We performed image-based high-content screening with a fluorogenic bioprobe (SF44), which visualizes cellular lipid droplets (LDs), to identify initial hit compounds. A structure-activity relationship study led us to yield a bioactive compound SB1501, which reduces cellular LDs in 3T3-L1 adipocytes without cytotoxicity. SB1501 induced the expression of gene products that regulate mitochondrial biogenesis and fatty acid oxidation in 3T3-L1 adipocytes. Daily treatment with SB1501 improved the metabolic states of db/db mice by reducing body fat mass, adipose tissue mass, food intake, and increasing glucose tolerance. The anti-obesity effect of SB1501 may result from perturbation of the PGC-1α-UCP1 regulatory axis in inguinal white adipose tissue and brown adipose tissue. These data suggest the therapeutic potential of SB1501 as an anti-obesity agent via modulating mitochondrial activities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cmdc.202100062DOI Listing
April 2021

NF-κB-inducing kinase maintains T cell metabolic fitness in antitumor immunity.

Nat Immunol 2021 02 4;22(2):193-204. Epub 2021 Jan 4.

Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Metabolic reprograming toward aerobic glycolysis is a pivotal mechanism shaping immune responses. Here we show that deficiency in NF-κB-inducing kinase (NIK) impairs glycolysis induction, rendering CD8 effector T cells hypofunctional in the tumor microenvironment. Conversely, ectopic expression of NIK promotes CD8 T cell metabolism and effector function, thereby profoundly enhancing antitumor immunity and improving the efficacy of T cell adoptive therapy. NIK regulates T cell metabolism via a NF-κB-independent mechanism that involves stabilization of hexokinase 2 (HK2), a rate-limiting enzyme of the glycolytic pathway. NIK prevents autophagic degradation of HK2 through controlling cellular reactive oxygen species levels, which in turn involves modulation of glucose-6-phosphate dehydrogenase (G6PD), an enzyme that mediates production of the antioxidant NADPH. We show that the G6PD-NADPH redox system is important for HK2 stability and metabolism in activated T cells. These findings establish NIK as a pivotal regulator of T cell metabolism and highlight a post-translational mechanism of metabolic regulation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41590-020-00829-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855506PMC
February 2021

The adaptor protein APPL2 controls glucose-stimulated insulin secretion via F-actin remodeling in pancreatic β-cells.

Proc Natl Acad Sci U S A 2020 11 29;117(45):28307-28315. Epub 2020 Oct 29.

Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong, China;

Filamentous actin (F-actin) cytoskeletal remodeling is critical for glucose-stimulated insulin secretion (GSIS) in pancreatic β-cells, and its dysregulation causes type 2 diabetes. The adaptor protein APPL1 promotes first-phase GSIS by up-regulating soluble -ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein expression. However, whether APPL2 (a close homology of APPL1 with the same domain organization) plays a role in β-cell functions is unknown. Here, we show that APPL2 enhances GSIS by promoting F-actin remodeling via the small GTPase Rac1 in pancreatic β-cells. β-cell specific abrogation of APPL2 impaired GSIS, leading to glucose intolerance in mice. APPL2 deficiency largely abolished glucose-induced first- and second-phase insulin secretion in pancreatic islets. Real-time live-cell imaging and phalloidin staining revealed that APPL2 deficiency abolished glucose-induced F-actin depolymerization in pancreatic islets. Likewise, knockdown of APPL2 expression impaired glucose-stimulated F-actin depolymerization and subsequent insulin secretion in INS-1E cells, which were attributable to the impairment of Ras-related C3 botulinum toxin substrate 1 (Rac1) activation. Treatment with the F-actin depolymerization chemical compounds or overexpression of gelsolin (a F-actin remodeling protein) rescued APPL2 deficiency-induced defective GSIS. In addition, APPL2 interacted with Rac GTPase activating protein 1 (RacGAP1) in a glucose-dependent manner via the bin/amphiphysin/rvs-pleckstrin homology (BAR-PH) domain of APPL2 in INS-1E cells and HEK293 cells. Concomitant knockdown of RacGAP1 expression reverted APPL2 deficiency-induced defective GSIS, F-actin remodeling, and Rac1 activation in INS-1E cells. Our data indicate that APPL2 interacts with RacGAP1 and suppresses its negative action on Rac1 activity and F-actin depolymerization thereby enhancing GSIS in pancreatic β-cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1073/pnas.2016997117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7668165PMC
November 2020

Author's Reply to Heart Transplantation to Fulminant Myocarditis during COVID-19 Outbreak.

Korean Circ J 2020 Nov;50(11):1041-1042

Department of Cardiothoracic Surgery, Keimyung University Dongsan Hospital, Keimyung University School of Medicine, Daegu, Korea.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4070/kcj.2020.3571DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7596211PMC
November 2020

Depletion of Adipocyte Leads to Lipodystrophy and Metabolic Dysregulation.

Diabetes 2021 01 12;70(1):182-195. Epub 2020 Oct 12.

Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of Korea

/ is a core component of the class III phosphatidylinositol 3-kinase required for autophagosome formation and vesicular trafficking. Although has been implicated in numerous diseases such as cancer, aging, and neurodegenerative disease, the role of in white adipose tissue and related metabolic diseases remains elusive. In this study, we show that adipocyte-specific knockout mice develop severe lipodystrophy, leading to adipose tissue inflammation, hepatic steatosis, and insulin resistance. Ablation of in adipocytes stimulates programmed cell death in a cell-autonomous manner, accompanied by elevated endoplasmic reticulum (ER) stress gene expression. Furthermore, we observed that depletion sensitized mature adipocytes to ER stress, leading to accelerated cell death. Taken together, these data suggest that adipocyte would serve as a crucial player for adipocyte survival and adipose tissue homeostasis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2337/db19-1239DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7881852PMC
January 2021

Successful Heart Transplantation to a Fulminant Myocarditis Patient during COVID-19 Outbreak - Lessons Learned.

Korean Circ J 2020 Jul;50(7):634-637

Department of Cardiothoracic Surgery, Keimyung University Dongsan Hospital, Keimyung University School of Medicine, Daegu, Korea.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4070/kcj.2020.0177DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7321758PMC
July 2020

Multimodality Imaging Guidance in Fulminant Myocarditis: When Endomyocardial Biopsy Is Not Amenable.

J Cardiovasc Imaging 2020 Oct 24;28(4):293-295. Epub 2020 Apr 24.

Division of Cardiology, Department of Internal Medicine, Cardiovascular Center, Keimyung University Dongsan Hospital, Daegu, Korea.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4250/jcvi.2019.0112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7572255PMC
October 2020

Neddylation of sterol regulatory element-binding protein 1c is a potential therapeutic target for nonalcoholic fatty liver treatment.

Cell Death Dis 2020 04 24;11(4):283. Epub 2020 Apr 24.

Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.

Nonalcoholic fatty liver disease (NAFLD) is a risk factor for progression of steatohepatitis, liver cirrhosis, and liver cancer. Although pathological condition of NAFLD, which arises from an excessive accumulation of triglyceride in the liver, is accompanied by elevated sterol regulatory element-binding protein 1c (SREBP1c) level, it is largely unknown which factors are involved in the modification of SREBP1c. In this study, we discovered that neddylation of SREBP1c competes with its ubiquitination and stabilizes SREBP1c protein level, and eventually promotes hepatic steatosis. We also demonstrated that human homolog of mouse double minute 2 (HDM2) acts as an E3 neddylation ligase of SREBP1c. Further, treatment with the neddylation inhibitor, MLN4924, attenuates high-fat diet-induced hepatic steatosis by reducing the levels of SREBP1c protein and hepatic triglyceride. Our results indicate that the blockade of SREBP1c neddylation could be a novel approach in the defense against NAFLD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41419-020-2472-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7181738PMC
April 2020

Hypoxia-inducible factors: new strategies for treatment of obesity-induced metabolic diseases.

Postgrad Med J 2020 08 16;96(1138):451-452. Epub 2020 Apr 16.

Institute of Molecular Biology and Genetics, Department of Biological Sciences, Seoul National University, Seoul, Korea (the Republic of)

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/postgradmedj-2019-136428DOI Listing
August 2020

Spatiotemporal contact between peroxisomes and lipid droplets regulates fasting-induced lipolysis via PEX5.

Nat Commun 2020 Jan 29;11(1):578. Epub 2020 Jan 29.

National Creative Research Initiatives Center for Adipose Tissue Remodeling, Institute of Molecular Biology and Genetics, Department of Biological Sciences, Seoul National University, Seoul, South Korea.

Lipid droplets (LDs) are key subcellular organelles for regulating lipid metabolism. Although several subcellular organelles participate in lipid metabolism, it remains elusive whether physical contacts between subcellular organelles and LDs might be involved in lipolysis upon nutritional deprivation. Here, we demonstrate that peroxisomes and peroxisomal protein PEX5 mediate fasting-induced lipolysis by stimulating adipose triglyceride lipase (ATGL) translocation onto LDs. During fasting, physical contacts between peroxisomes and LDs are increased by KIFC3-dependent movement of peroxisomes toward LDs, which facilitates spatial translocations of ATGL onto LDs. In addition, PEX5 could escort ATGL to contact points between peroxisomes and LDs in the presence of fasting cues. Moreover, in adipocyte-specific PEX5-knockout mice, the recruitment of ATGL onto LDs was defective and fasting-induced lipolysis is attenuated. Collectively, these data suggest that physical contacts between peroxisomes and LDs are required for spatiotemporal translocation of ATGL, which is escorted by PEX5 upon fasting, to maintain energy homeostasis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-019-14176-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6989686PMC
January 2020

Two Faces of White Adipose Tissue with Heterogeneous Adipogenic Progenitors.

Diabetes Metab J 2019 12;43(6):752-762

National Creative Research Initiatives Center for Adipose Tissue Remodeling, Institute of Molecular Biology and Genetics, Department of Biological Sciences, Seoul National University, Seoul, Korea.

Chronic energy surplus increases body fat, leading to obesity. Since obesity is closely associated with most metabolic complications, pathophysiological roles of adipose tissue in obesity have been intensively studied. White adipose tissue is largely divided into subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT). These two white adipose tissues are similar in their appearance and lipid storage functions. Nonetheless, emerging evidence has suggested that SAT and VAT have different characteristics and functional roles in metabolic regulation. It is likely that there are intrinsic differences between VAT and SAT. In diet-induced obese animal models, it has been reported that adipogenic progenitors in VAT rapidly proliferate and differentiate into adipocytes. In obesity, VAT exhibits elevated inflammatory responses, which are less prevalent in SAT. On the other hand, SAT has metabolically beneficial effects. In this review, we introduce recent studies that focus on cellular and molecular components modulating adipogenesis and immune responses in SAT and VAT. Given that these two fat depots show different functions and characteristics depending on the nutritional status, it is feasible to postulate that SAT and VAT have different developmental origins with distinct adipogenic progenitors, which would be a key determining factor for the response and accommodation to metabolic input for energy homeostasis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4093/dmj.2019.0174DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6943255PMC
December 2019

Activation of invariant natural killer T cells stimulates adipose tissue remodeling via adipocyte death and birth in obesity.

Genes Dev 2019 12 14;33(23-24):1657-1672. Epub 2019 Nov 14.

National Creative Research Initiatives Center for Adipose Tissue Remodeling, Institute of Molecular Biology and Genetics, Department of Biological Sciences, Seoul National University, Seoul 08826, South Korea.

In obesity, adipose tissue undergoes dynamic remodeling processes such as adipocyte hypertrophy, hypoxia, immune responses, and adipocyte death. However, whether and how invariant natural killer T (iNKT) cells contribute to adipose tissue remodeling are elusive. In this study, we demonstrate that iNKT cells remove unhealthy adipocytes and stimulate the differentiation of healthy adipocytes. In obese adipose tissue, iNKT cells were abundantly found nearby dead adipocytes. FasL-positive adipose iNKT cells exerted cytotoxic effects to eliminate hypertrophic and pro-inflammatory Fas-positive adipocytes. Furthermore, in vivo adipocyte-lineage tracing mice model showed that activation of iNKT cells by alpha-galactosylceramide promoted adipocyte turnover, eventually leading to potentiation of the insulin-dependent glucose uptake ability in adipose tissue. Collectively, our data propose a novel role of adipose iNKT cells in the regulation of adipocyte turnover in obesity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1101/gad.329557.119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6942052PMC
December 2019

RNF20 Functions as a Transcriptional Coactivator for PPARγ by Promoting NCoR1 Degradation in Adipocytes.

Diabetes 2020 01 11;69(1):20-34. Epub 2019 Oct 11.

National Creative Research Initiatives Center for Adipose Tissue Remodeling, Institute of Molecular Biology and Genetics, Department of Biological Sciences, Seoul National University, Seoul, Korea

Adipose tissue is the key organ coordinating whole-body energy homeostasis. Although it has been reported that ring finger protein 20 (RNF20) regulates lipid metabolism in the liver and kidney, the roles of RNF20 in adipose tissue have not been explored. Here, we demonstrate that RNF20 promotes adipogenesis by potentiating the transcriptional activity of peroxisome proliferator-activated receptor-γ (PPARγ). Under normal chow diet feeding, defective ( ) mice exhibited reduced fat mass with smaller adipocytes compared with wild-type littermates. In addition, high-fat diet-fed mice alleviated systemic insulin resistance accompanied by a reduced expansion of fat tissue. Quantitative proteomic analyses revealed significantly decreased levels of PPARγ target proteins in adipose tissue of mice. Mechanistically, RNF20 promoted proteasomal degradation of nuclear corepressor 1 (NCoR1), which led to stimulation of the transcriptional activity of PPARγ. Collectively, these data suggest that RNF20-NCoR1 is a novel axis in adipocyte biology through fine-tuning the transcriptional activity of PPARγ.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2337/db19-0508DOI Listing
January 2020

TonEBP/NFAT5 promotes obesity and insulin resistance by epigenetic suppression of white adipose tissue beiging.

Nat Commun 2019 08 6;10(1):3536. Epub 2019 Aug 6.

School of Life Sciences, Ulsan National Institute of Science and Technology, Ulsan, 44919, Republic of Korea.

Tonicity-responsive enhancer binding protein (TonEBP or NFAT5) is a regulator of cellular adaptation to hypertonicity, macrophage activation and T-cell development. Here we report that TonEBP is an epigenetic regulator of thermogenesis and obesity. In mouse subcutaneous adipocytes, TonEBP expression increases > 50-fold in response to high-fat diet (HFD) feeding. Mice with TonEBP haplo-deficiency or adipocyte-specific TonEBP deficiency are resistant to HFD-induced obesity and metabolic defects (hyperglycemia, hyperlipidemia, and hyperinsulinemia). They also display increased oxygen consumption, resistance to hypothermia, and beiging of subcutaneous fat tissues. TonEBP suppresses the promoter of β3-adrenoreceptor gene, a critical regulator of lipolysis and thermogenesis, in ex vivo and cultured adipocytes. This involves recruitment of DNMT1 DNA methylase and methylation of the promoter. In human subcutaneous adipocytes TonEBP expression displays a correlation with body mass index but an inverse correlation with β3-adrenoreceptor expression. Thus, TonEBP is an attractive therapeutic target for obesity, insulin resistance, and hyperlipidemia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-019-11302-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6684655PMC
August 2019

During Adipocyte Remodeling, Lipid Droplet Configurations Regulate Insulin Sensitivity through F-Actin and G-Actin Reorganization.

Mol Cell Biol 2019 10 27;39(20). Epub 2019 Sep 27.

National Creative Research Initiatives Center for Adipose Tissue Remodeling, Department of Biological Sciences, Institute of Molecular Biology and Genetics, Seoul National University, Seoul, South Korea

Adipocytes have unique morphological traits in insulin sensitivity control. However, how the appearance of adipocytes can determine insulin sensitivity has not been understood. Here, we demonstrate that actin cytoskeleton reorganization upon lipid droplet (LD) configurations in adipocytes plays important roles in insulin-dependent glucose uptake by regulating GLUT4 trafficking. Compared to white adipocytes, brown/beige adipocytes with multilocular LDs exhibited well-developed filamentous actin (F-actin) structure and potentiated GLUT4 translocation to the plasma membrane in the presence of insulin. In contrast, LD enlargement and unilocularization in adipocytes downregulated cortical F-actin formation, eventually leading to decreased F-actin-to-globular actin (G-actin) ratio and suppression of insulin-dependent GLUT4 trafficking. Pharmacological inhibition of actin polymerization accompanied with impaired F/G-actin dynamics reduced glucose uptake in adipose tissue and conferred systemic insulin resistance in mice. Thus, our study reveals that adipocyte remodeling with different LD configurations could be an important factor to determine insulin sensitivity by modulating F/G-actin dynamics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1128/MCB.00210-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6766695PMC
October 2019

Ventricular Septal Defect Closure in a Neonate with Osteogenesis Imperfecta.

Korean J Thorac Cardiovasc Surg 2019 Jun 5;52(3):162-164. Epub 2019 Jun 5.

Department of Thoracic and Cardiovascular Surgery, Keimyung University Dongsan Medical Center, Keimyung University School of Medicine, Daegu, Korea.

A male patient weighing 2.5 kg was admitted for respiratory difficulty, and a large ventricular septal defect (VSD) was diagnosed. During care, sudden right leg swelling with a femur shaft fracture occurred. The patient's father had a history of recurrent lower extremity fractures; thus, osteogenesis imperfecta was considered. The patient's respiratory difficulty became aggravated, and VSD repair in the neonatal period was therefore performed with gentle sternal traction and great vessel manipulation under total intravenous anesthesia to prevent malignant hyperthermia. The patient was discharged without notable problems, except minor wound dehiscence. Outpatient genetic testing revealed that the patient had a mutation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5090/kjtcs.2019.52.3.162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6559185PMC
June 2019

GABA-stimulated adipose-derived stem cells suppress subcutaneous adipose inflammation in obesity.

Proc Natl Acad Sci U S A 2019 06 3;116(24):11936-11945. Epub 2019 Jun 3.

National Creative Research Initiatives Center for Adipose Tissue Remodeling, Institute of Molecular Biology and Genetics, Department of Biological Sciences, Seoul National University, 08826 Seoul, South Korea;

Accumulating evidence suggests that subcutaneous and visceral adipose tissues are differentially associated with metabolic disorders. In obesity, subcutaneous adipose tissue is beneficial for metabolic homeostasis because of repressed inflammation. However, the underlying mechanism remains unclear. Here, we demonstrate that γ-aminobutyric acid (GABA) sensitivity is crucial in determining fat depot-selective adipose tissue macrophage (ATM) infiltration in obesity. In diet-induced obesity, GABA reduced monocyte migration in subcutaneous inguinal adipose tissue (IAT), but not in visceral epididymal adipose tissue (EAT). Pharmacological modulation of the GABA receptor affected the levels of ATM infiltration and adipose tissue inflammation in IAT, but not in EAT, and GABA administration ameliorated systemic insulin resistance and enhanced insulin-dependent glucose uptake in IAT, accompanied by lower inflammatory responses. Intriguingly, compared with adipose-derived stem cells (ADSCs) from EAT, IAT-ADSCs played key roles in mediating GABA responses that repressed ATM infiltration in high-fat diet-fed mice. These data suggest that selective GABA responses in IAT contribute to fat depot-selective suppression of inflammatory responses and protection from insulin resistance in obesity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1073/pnas.1822067116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6575165PMC
June 2019

Impact of volume reduction in giant left atrium during surgical ablation of atrial fibrillation.

J Thorac Dis 2019 Jan;11(1):84-92

Department of Cardiology, Sejong Heart Institute, Sejong General Hospital, Bucheon, Republic of Korea.

Background: An enlarged left atrium (LA) is a well-known risk factor for ablation failure of atrial fibrillation (AF). We analyzed the result of concomitant AF ablation in patients with a giant LA and evaluated the effect of LA volume reduction.

Methods: Between 2000 and 2011, 116 patients with a giant LA (antero-posterior dimension ≥70 mm) who underwent surgical AF ablation during MV surgery were retrospectively reviewed. Among these, 28 patients received aggressive LA volume reduction procedure (reduction group) while the other 88 patients received the surgery without LA volume reduction (non-reduction group). Mean follow-up duration was 6.8±3.0 years.

Results: Aortic clamping and cardio-pulmonary bypass times were significantly longer in reduction group than non-reduction group (P<0.001 and 0.025, respectively). There were no significant differences in early mortality rates (3.7% 5.7%, P>0.99) and major complication rates. Rates of freedom from AF at 1, 3 and 5 years were 84.2%, 74.3% and 54.5%, respectively in reduction group and 49.0%, 33.2% and 28.4%, respectively in non-reduction group (P=0.013). Multivariable analysis revealed severe pulmonary hypertension as an independent risk factor for AF recurrence (HR, 15.9; 95% CI, 1.69-149.54, P=0.015) while LA volume reduction (HR, 0.50; 95% CI, 0.28-0.89, P=0.018) and the use of cryoablation instead of radiofrequency (HR, 0.11; 95% CI, 0.01-0.95, P=0.045) were found to be protective against AF recurrence.

Conclusions: Aggressive LA volume reduction was found to improve rhythm outcomes in patients with a giant LA undergoing surgical AF ablation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/jtd.2018.12.118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6384332PMC
January 2019

Evaluation of the Hot Workability of Commercially Pure Ti Using Hot Torsion Tests.

J Nanosci Nanotechnol 2019 Mar;19(3):1772-1776

Department of Materials Science and Engineering, Inha University, Incheon, 22212, Republic of Korea.

Optimum processing conditions were obtained by evaluating the hot working behavior of commercially pure Ti using hot torsion tests. Hot torsion tests were conducted at temperatures ranging from 800 °C-1000 °C and strain rates ranging from 0.1-10 s. The flow curves show that the peak stress increases as the temperature decreases and the strain rate increases. The optimum processing conditions were derived by comparing the processing and activation energy maps. The microstructure was characterized based on various regions of the processing map. The activation energy for plastic deformation was obtained using the constitutive equation. The activation energy differs depending on the constituent phases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1166/jnn.2019.16181DOI Listing
March 2019

Brazing Characteristics and Bonding Strength of Pure Titanium Joints Brazed with Low-Melting Temperature Zi-17Ti-22Ni Filler Metal.

J Nanosci Nanotechnol 2019 Mar;19(3):1592-1596

Inha University, Incheon 22212, Republic of Korea.

The brazing characteristics and bonding strengths of pure titanium joints are evaluated for joints brazed with Zr-17Ti-22Ni filler. Vacuum brazing was conducted at temperatures between the melting temperatures of the filler metals and the beta-transition temperature of pure titanium at 3 MPa of pressure for 5 min. Fracturing of the pure titanium joint brazed at 1,093 K occurred before yielding during the tensile tests owing to the presence of a serious segregation region containing harder and more brittle [Ti, Zr]2Ni intermetallic compounds. In contrast, in pure titanium joints brazed at and above 1,113 K, fracturing occurred at the base metal. The yield strengths of the samples brazed at 1,113 K-1,133 K were estimated to be in the range of 320-350 MPa and the ultimate tensile strengths likewise ranged from 350 to 380 MPa. The strength of pure titanium brazed at 1,153 K decreased rapidly. The results of this study show that the optimum temperature to ensure good performance after the brazing of pure titanium with Zr-17Ti-22Ni as a filler metal ranges from 1,113 K to 1,133 K.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1166/jnn.2019.16158DOI Listing
March 2019

The Brain Donation Program in South Korea.

Yonsei Med J 2018 Dec;59(10):1197-1204

Department of Neurology, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, Korea.

Purpose: Obtaining brain tissue is critical to definite diagnosis and to furthering understanding of neurodegenerative diseases. The present authors have maintained the National Neuropathology Reference and Diagnostic Laboratories for Dementia in South Korea since 2016. We have built a nationwide brain bank network and are collecting brain tissues from patients with neurodegenerative diseases. We are aiming to facilitate analyses of clinic-pathological and image-pathological correlations of neurodegenerative disease and to broaden understanding thereof.

Materials And Methods: We recruited participants through two routes: from memory clinics and the community. As a baseline evaluation, clinical interviews, a neurological examination, laboratory tests, neuropsychological tests, and MRI were undertaken. Some patients also underwent amyloid PET.

Results: We recruited 105 participants, 70 from clinics and 35 from the community. Among them, 11 died and were autopsied. The clinical diagnoses of the autopsied patients included four with Alzheimer's disease (AD), two with subcortical vascular dementia, two with non-fluent variant primary progressive aphasia, one with leukoencephalopathy, one with frontotemporal dementia (FTD), and one with Creutzfeldt-Jakob disease (CJD). Five patients underwent amyloid PET: two with AD, one with mixed dementia, one with FTD, and one with CJD.

Conclusion: The clinical and neuropathological information to be obtained from this cohort in the future will provide a deeper understanding of the neuropathological mechanisms of cognitive impairment in Asia, especially Korea.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3349/ymj.2018.59.10.1197DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6240560PMC
December 2018

Hypoxia Restrains Lipid Utilization via Protein Kinase A and Adipose Triglyceride Lipase Downregulation through Hypoxia-Inducible Factor.

Mol Cell Biol 2019 01 3;39(2). Epub 2019 Jan 3.

National Creative Research Initiatives Center for Adipose Tissue Remodeling, Institute of Molecular Biology and Genetics, Department of Biological Sciences, Seoul National University, Seoul, South Korea

Oxygen is a key molecule for efficient energy production in living organisms. Although aerobic organisms have adaptive processes to survive in low-oxygen environments, it is poorly understood how lipolysis, the first step of energy production from stored lipid metabolites, would be modulated during hypoxia. Here, we demonstrate that fasting-induced lipolysis is downregulated by hypoxia through the hypoxia-inducible factor (HIF) signaling pathway. In and mammalian adipocytes, hypoxia suppressed protein kinase A (PKA)-stimulated lipolysis, which is evolutionarily well conserved. During hypoxia, the levels of PKA activity and adipose triglyceride lipase (ATGL) protein were downregulated, resulting in attenuated fasting-induced lipolysis. In worms, HIF stabilization was sufficient to moderate the suppressive effect of hypoxia on lipolysis through ATGL and PKA inhibition. These data suggest that HIF activation under hypoxia plays key roles in the suppression of lipolysis, which might preserve energy resources in both and mammalian adipocytes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1128/MCB.00390-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6321877PMC
January 2019

Hypothalamic Macrophage Inducible Nitric Oxide Synthase Mediates Obesity-Associated Hypothalamic Inflammation.

Cell Rep 2018 10;25(4):934-946.e5

Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Ulsan College of Medicine, Seoul 05505, Korea. Electronic address:

Obesity-associated metabolic alterations are closely linked to low-grade inflammation in peripheral organs, in which macrophages play a central role. Using genetic labeling of myeloid lineage cells, we show that hypothalamic macrophages normally reside in the perivascular area and circumventricular organ median eminence. Chronic consumption of a high-fat diet (HFD) induces expansion of the monocyte-derived macrophage pool in the hypothalamic arcuate nucleus (ARC), which is significantly attributed to enhanced proliferation of macrophages. Notably, inducible nitric oxide synthase (iNOS) is robustly activated in ARC macrophages of HFD-fed obese mice. Hypothalamic macrophage iNOS inhibition completely abrogates macrophage accumulation and activation, proinflammatory cytokine overproduction, reactive astrogliosis, blood-brain-barrier permeability, and lipid accumulation in the ARC of obese mice. Moreover, central iNOS inhibition improves obesity-induced alterations in systemic glucose metabolism without affecting adiposity. Our findings suggest a critical role for hypothalamic macrophage-expressed iNOS in hypothalamic inflammation and abnormal glucose metabolism in cases of overnutrition-induced obesity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.celrep.2018.09.070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6284237PMC
October 2018

SREBP1c-PAX4 Axis Mediates Pancreatic β-Cell Compensatory Responses Upon Metabolic Stress.

Diabetes 2019 01 23;68(1):81-94. Epub 2018 Oct 23.

National Creative Research Initiatives Center for Adipose Tissue Remodeling, Institute of Molecular Biology and Genetics, Department of Biological Sciences, Seoul National University, Seoul, South Korea

SREBP1c is a key transcription factor for de novo lipogenesis. Although SREBP1c is expressed in pancreatic islets, its physiological roles in pancreatic β-cells are largely unknown. In this study, we demonstrate that SREBP1c regulates β-cell compensation under metabolic stress. SREBP1c expression level was augmented in pancreatic islets from obese and diabetic animals. In pancreatic β-cells, SREBP1c activation promoted the expression of cell cycle genes and stimulated β-cell proliferation through its novel target gene, Compared with mice, mice showed glucose intolerance with low insulin levels. Moreover, β-cells from mice exhibited reduced capacity to proliferate and secrete insulin. Conversely, transplantation of SREBP1c-overexpressing islets restored insulin levels and relieved hyperglycemia in streptozotocin-induced diabetic animals. Collectively, these data suggest that pancreatic SREBP1c is a key player in mediating β-cell compensatory responses in obesity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2337/db18-0556DOI Listing
January 2019

Effects of Three Thiazolidinediones on Metabolic Regulation and Cold-Induced Thermogenesis.

Mol Cells 2018 Oct;41(10):900-908

National Creative Research Initiatives Center for Adipose Tissue Remodeling, Institute of Molecular Biology and Genetics, Department of Biological Sciences, Seoul National University, Seoul 08826, Korea.

Insulin resistance is closely associated with metabolic diseases such as type 2 diabetes, dyslipidemia, hypertension and atherosclerosis. Thiazolidinediones (TZDs) have been developed to ameliorate insulin resistance by activation of peroxisome proliferator-activated receptor (PPAR) γ. Although TZDs are synthetic ligands for PPARγ, metabolic outcomes of each TZD are different. Moreover, there are lack of head-to-head comparative studies among TZDs in the aspect of metabolic outcomes. In this study, we analyzed the effects of three TZDs, including lobeglitazone (Lobe), rosiglitazone (Rosi), and pioglitazone (Pio) on metabolic and thermogenic regulation. In adipocytes, Lobe more potently stimulated adipogenesis and insulin-dependent glucose uptake than Rosi and Pio. In the presence of pro-inflammatory stimuli, Lobe efficiently suppressed expressions of pro-inflammatory genes in macrophages and adipocytes. In obese and diabetic mice, Lobe effectively promoted insulin-stimulated glucose uptake and suppressed pro-inflammatory responses in epididymal white adipose tissue (EAT), leading to improve glucose intolerance. Compared to other two TZDs, Lobe enhanced beige adipocyte formation and thermogenic gene expression in inguinal white adipose tissue (IAT) of lean mice, which would be attributable to cold-induced thermogenesis. Collectively, these comparison data suggest that Lobe could relieve insulin resistance and enhance thermogenesis at low-concentration conditions where Rosi and Pio are less effective.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.14348/molcells.2018.0294DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6199571PMC
October 2018

Corrigendum to "Carbonyl reductase 1 protects pancreatic ß-cells against oxidative stress-induced apoptosis in glucotoxicity and glucolipotoxicity" [Free Radic. Biol. Med. 49 (2010):1522-1533].

Free Radic Biol Med 2018 12 31;129:614-617. Epub 2018 Jul 31.

Medical Science and Engineering Research Center for Bioreaction to Reactive Oxygen Species and Biomedical Science Institute (BK-21), Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, #1, Hoegi-dong, Dongdaemoon-gu, Seoul 130-701, Republic of Korea. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.freeradbiomed.2018.07.011DOI Listing
December 2018