• IMMUNE NETWORK
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• 제22권5호
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• pp.43.1-43.12
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• 2022

Osteoclasts (OCs) are clinically important cells that resorb bone matrix. Accelerated bone destruction by OCs is closely linked to the development of metabolic bone diseases. In this study, we screened novel chemical inhibitors targeting OC differentiation to identify drug candidates for metabolic bone diseases. We identified that 1,3-dibenzyl-5-fluorouracil, also named OCI-101, is a novel inhibitor of osteoclastogenesis. The formation of multinucleated OCs is reduced by treatment with OCI-101 in a dose-dependent manner. OCI-101 inhibited the expression of OC markers via downregulation of receptor activator of NF-κB ligand and M-CSF signaling pathways. Finally, we showed that OCI-101 prevents ovariectomy-induced bone loss by suppressing OC differentiation in mice. Hence, these results demonstrated that OCI-101 is a good drug candidate for treating metabolic bone diseases.

• 대한의생명과학회지
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• 제26권4호
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• pp.368-375
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• 2020

Metabolic syndrome (MetS) is a disease that is accompanied by various metabolic related problems and refers to a disease in which various adult diseases occur along with obesity. These metabolic syndromes appear according to the individual's genetic background. APOA5-ZPR1-BUD13, a gene cluster belonging to chromosome 11q23.3, is well known for its risk of plasma triglycerides and coronary artery disease. Recently, the GWAS results for metabolic syndrome were published in Koreans. The results included the APOA5-ZPR1-BUD13, and the SNPs that first appeared in Koreans in the ZPR1 and BUD13 were also discovered. In this study, the reproducibility was investigated for the newly discovered ZPR1 (rs964184) and BUD13 (rs2075295, rs1558861) using The Health Examinees (HEXA) cohort and showed significance. In addition, BUD13 (rs117548857, rs10488698, rs149527022, rs10790162), ZPR1 (rs2075290, rs145796806, rs201247587), APOA5 (rs12791103, rs1263173, rs7396835, rs17520254) were additionally discovered and significant results were obtained. For the SNPs that showed significant results, the effect on protein expression and the effect of expression quantitative trait loci (eQTL) were also confirmed. This study is expected to contribute to the prevention and treatment of diseases with differences in onset based on individual genetic patterns as well as presenting the effect of genetic mutations in the APOA5-ZPR1-BUD13 on metabolic syndrome and blood lipid levels.

• 한국학교ㆍ지역보건교육학회지
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• 제23권1호
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• pp.29-40
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• 2022

Objectives: The purpose of this study is to identify the relationship between metabolic syndrome factor diseases and falls in the elderly aged 65 years or older and use them as basic data to reduce the risk of falls. Methods: The method of this study was to compare the injury-related characteristics of the fall and non-fall groups with a factor disease of metabolic syndrome in Korea over 65 years of age. Data from the 14th National Hospital Discharge In-depth Injury Survey in 2018 were used to conduct the study. A total of 7,991 data were analyzed using SPSS 23.0. Results: Among the total injuries, the fall group with metabolic syndrome factor disease accounted for 69.0% and the non-fall group 31.0%. Falls occurred in 86.3% of households. In the fall group with metabolic syndrome factor disease, the number of females was 1.9~2.1 times higher than that of males. Compared to 65~69 years of age, the incidence of falls was 1.4~1.5 times higher in 70~79 years, 1.7~2.2 times higher in 80~89 years, and 2.5~3.6 times higher in 90-year-olds and older. In NISS, the incidence of falls was 1.7 times higher in moderate compared to mild. In principle diagnosis, the incidence of falls was 2.2 times higher in S40-S99 compared to S00-S19. Conclusion: The elderly with metabolic syndrome factor disease should continue to promote health through light exercise that can strengthen muscle strength to prevent falls.

• Molecules and Cells
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• 제28권2호
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• pp.75-80
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• 2009

The cyclic environmental conditions brought about by the 24 h rotation of the earth have allowed the evolution of endogenous circadian clocks that control the temporal alignment of behaviour and physiology, including the uptake and processing of nutrients. Both metabolic and circadian regulatory systems are built upon a complex feedback network connecting centres of the central nervous system and different peripheral tissues. Emerging evidence suggests that circadian clock function is closely linked to metabolic homeostasis and that rhythm disruption can contribute to the development of metabolic disease. At the same time, metabolic processes feed back into the circadian clock, affecting clock gene expression and timing of behaviour. In this review, we summarize the experimental evidence for this bimodal interaction, with a focus on the molecular mechanisms mediating this exchange, and outline the implications for clock-based and metabolic diseases.

• Journal of Preventive Medicine and Public Health
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• 제23권3호
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• pp.345-357
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• 1990

Accumulated data on medical care utilization among the insured in Korea Medical Insurance Corporation can explain the health status of the population. The purpose of this study was to analyze a change of the disease-mix and utilization pattern by controlling the size of the population enrollment. Major findings of the study are as follows : 1. The changes of inpatient disease-mix a. Utilization rate was 139.2% in 1988 against 1980. b. Disease groups higher than the average utilization rate included neoplasms, endocrine, nutritional and metabolic diseases and immunity disorders, mental disorders etc. Meanwhile, disease groups seen less often were infections and parasistic diseases, diseases of blood and bloodforming, diseases of the digestive system etc. c. Utilization rate was up 106.3% in 1988 compared to 1985, and diseases above that average level were ill-defined intestinal infections, chronic liver disease and cirrhosis, diabetes mellitus, essential hypertension, etc. d. The disease-mix by institution in 1988 compared to 1985 shows that chronic disorders rank high in general hospitals whereas opthalmologic, obstetric, and orthopedic diseases rank high in private clinics. 2. The changes of outpatient disease-mix a. Utilization rate was up 175.2% in 1988 compared to 1980. b. Disease groups higher than the average utilization rate included neoplasms, endocrine, nutritional and metabolic diseases and immunity disorders, mental disorders etc. And disease groups seen less often were infections and parasistic diseases, diseases of the respiratory system, diseases of the genitourinary system. etc. c. Utilization rate was up 104.0% in 1988 compared to 1985, and diseases above that average level were gastric ulcer, diseases of hard tissues of teeth, etc. And diseases seen below that average level were acute nasopharyngitis(common cold). acute upper respiratory infections of multiple or unspecified sites, etc. It was concluded that medical care utilization level was increased, and that, from 1980 to 1988, disease-mix shifted to the chronic disorders. Chronic disorders accounted for more medical care utilization in general hospitals.

• 한방비만학회지
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• 제7권2호
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• pp.15-25
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• 2007

Objectives In clinical studies, the visceral fat obesity has been emphasized because of its correlation with the metabolic syndrome. But the subcutaneous adipose tissue also would correlate with the risk factor of metabolic syndrome. Especially deep tissue, which is a subdivision of the subcutaneous adipose tissue would be more related. This study is to investigate the relationship between subcutaneous adipose tissue and various diseases. Methods We searched for papers which had subcutaneous adipose tissue, deep subcutaneous adipose tissue and obesity for subjects in the Pubmed site. Results : 24 papers were found. Subcutaneous adipose tissue, deep subcutaneous adipose tissue especially, was related with the insulin resistance, metabolic syndrome, sex hormones and other diseases. Conclusions Subcutaneous adipose tissue is a risk factor of insulin resistance but not lipoprotein. But deep subcutaneous adipose tissue was related with lipoprotein. So deep tissue, which is a subdivision of the subcutaneous adipose tissue is a more important risk factor of the metabolic syndrome.

• Journal of mucopolysaccharidosis and rare diseases
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• 제1권2호
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• pp.44-48
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• 2015

Body fat distribution in patients with Prader-Willi syndrome (PWS) is characterized by reduce lean body mass (LBM), increased total body fat mass (FM), and lower percentage of visceral adipose tissue (VAT). Individuals with PWS seem to have a lower risk for insulin resistance with high levels of adiponectin, an anti-atherogenic adipocytokine that is decreased in visceral fat hypertrophy subjects compared to simple obese subjects, both in children and in adults. The mechanism of the reduction in visceral adiposity in PWS is still unclear. It might be related to qualitative intrinsic characteristics of adipocyte or novel genetic influences on the control of fat distribution. However, obesity remains a critical problem, and obesity status plays a crucial role in individual metabolic risk clustering and development of metabolic syndrome (Mets) in PWS children and adults. Long-term growth hormone (GH) treatment after cessation of skeletal growth improved body composition, with an increase in lean body mass and a reduction in total body fat and subcutaneous and visceral fat in PWS adults. Thus, the role of GH is important after childhood because it might attenuate obesity and Mets in PWS adult by adipocyte modification.

• Journal of Microbiology and Biotechnology
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• 제33권1호
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• pp.114-122
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• 2023

A family of signal transduction pathways known as wingless type (Wnt) signaling pathways is essential to developmental processes like cell division and proliferation. Mutation in Wnt signaling results in a variety of diseases, including cancers of the breast, colon, and skin, metabolic disease, and neurodegenerative disease; thus, the Wnt signaling pathways have been attractive targets for disease treatment. However, the complicatedness and large involveness of the pathway often hampers pinpointing the specific targets of the metabolic process. In our current study, we investigated the differential metabolic regulation by the overexpression of the Wnt signaling pathway in a timely-resolved manner by applying high-throughput and un-targeted metabolite profiling. We have detected and annotated 321 metabolite peaks from a total of 36 human embryonic kidney (HEK) 293 cells using GC-TOF MS and LC-Orbitrap MS. The un-targeted metabolomic analysis identified the radical reprogramming of a range of central carbon/nitrogen metabolism pathways, including glycolysis, TCA cycle, and glutaminolysis, and fatty acid pathways. The investigation, combined with targeted mRNA profiles, elucidated an explicit understanding of activated fatty acid metabolism (β-oxidation and biosynthesis). The findings proposed detailed mechanistic biochemical dynamics in response to Wnt-driven metabolic changes, which may help design precise therapeutic targets for Wnt-related diseases.

• BMB Reports
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• 제51권11호
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• pp.549-556
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• 2018

Mitochondria are ubiquitous and multi-functional organelles involved in diverse metabolic processes, namely energy production and biomolecule synthesis. The intracellular mitochondrial morphology and distribution change dynamically, which reflect the metabolic state of a given cell type. A dramatic change of the mitochondrial dynamics has been observed in early development that led to further investigations on the relationship between mitochondria and the process of development. A significant developmental process to focus on, in this review, is a differentiation of neural progenitor cells into neurons. Information on how mitochondria-regulated cellular energetics is linked to neuronal development will be discussed, followed by functions of mitochondria and associated diseases in neuronal development. Lastly, the potential use of mitochondrial features in analyzing various neurodevelopmental diseases will be addressed.

• BMB Reports
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• 제56권4호
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• pp.225-233
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• 2023

Hepatocellular carcinoma (HCC) is a very common form of cancer worldwide and is often fatal. Although the histopathology of HCC is characterized by metabolic pathophysiology, fibrosis, and cirrhosis, the focus of treatment has been on eliminating HCC. Recently, three-dimensional (3D) multicellular hepatic spheroid (MCHS) models have provided a) new therapeutic strategies for progressive fibrotic liver diseases, such as antifibrotic and anti-inflammatory drugs, b) molecular targets, and c) treatments for metabolic dysregulation. MCHS models provide a potent anti-cancer tool because they can mimic a) tumor complexity and heterogeneity, b) the 3D context of tumor cells, and c) the gradients of physiological parameters that are characteristic of tumors in vivo. However, the information provided by an multicelluar tumor spheroid (MCTS) model must always be considered in the context of tumors in vivo. This mini-review summarizes what is known about tumor HCC heterogeneity and complexity and the advances provided by MCHS models for innovations in drug development to combat liver diseases.