• Title/Summary/Keyword: Metabolic Targeting

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Comparison of Cardiovascular Health Status and Health Behaviors in Korean Women based on Household Income (소득수준에 따른 성인여성의 심혈관계 건강상태와 건강행위)

  • Park, Young-Joo;Shin, Nah-Mee;Yoon, Ji-Won;Choi, Ji-Won;Lee, Sook-Ja
    • Journal of Korean Academy of Nursing
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    • v.40 no.6
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    • pp.831-843
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    • 2010
  • Purpose: In this study cardiovascular health status and health behavior of Korean women based on their household income were explored. Methods: For this cross-sectional study, 91 women residing in the community were recruited to complete survey questionnaires and biophysical tests including blood pressure (BP), body mass index (BMI), body fat rate, waist circumference (WC), and blood chemistry tests. Results: Compared to non-low income women (NLIW), low income women (LIW) were more likely to be older, less educated, and jobless, and further more LIW were postmenopause and reported having been diagnosed with hypertension or hypercholesterolemia. Significant differences were found in systolic BP, triglyceride level, BMI, body fat rate, and WC between the groups. Two fifths of the LIW had indications for metabolic syndrome. Their 10-yr risk estimate of myocardioal infarction or coronary death demonstrated a higher probability than that of NLIW. Although these significant differences were due to age gap between the groups, advanced age is known to be one of the key characteristics of LIW as well as a non-modifiable risk factor. Conclusion: Effective community programs for vulnerable women at risk of cardiovascular disease should be based on strategies targeting unhealthy behaviors and modifiable risk factors.

A novel and safe small molecule enhances hair follicle regeneration by facilitating metabolic reprogramming

  • Son, Myung Jin;Jeong, Jae Kap;Kwon, Youjeong;Ryu, Jae-Sung;Mun, Seon Ju;Kim, Hye Jin;Kim, Sung-wuk;Yoo, Sanghee;Kook, Jiae;Lee, Hongbum;Kim, Janghwan;Chung, Kyung-Sook
    • Experimental and Molecular Medicine
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    • v.50 no.12
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    • pp.5.1-5.15
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    • 2018
  • Targeting hair follicle regeneration has been investigated for the treatment of hair loss, and fundamental studies investigating stem cells and their niche have been described. However, knowledge of stem cell metabolism and the specific regulation of bioenergetics during the hair regeneration process is currently insufficient. Here, we report the hair regrowth-promoting effect of a newly synthesized novel small molecule, IM176OUT05 (IM), which activates stem cell metabolism. IM facilitated stemness induction and maintenance during an induced pluripotent stem cell generation process. IM treatment mildly inhibited mitochondrial oxidative phosphorylation and concurrently increased glycolysis, which accelerated stemness induction during the early phase of reprogramming. More importantly, the topical application of IM accelerated hair follicle regeneration by stimulating the progression of the hair follicle cycle to the anagen phase and increased the hair follicle number in mice. Furthermore, the stem cell population with a glycolytic metabotype appeared slightly earlier in the IM-treated mice. Stem cell and niche signaling involved in the hair regeneration process was also activated by the IM treatment during the early phase of hair follicle regeneration. Overall, these results show that the novel small molecule IM promotes tissue regeneration, specifically in hair regrowth, by restructuring the metabolic configuration of stem cells.

An Essential Role of the N-Terminal Region of ACSL1 in Linking Free Fatty Acids to Mitochondrial β-Oxidation in C2C12 Myotubes

  • Nan, Jinyan;Lee, Ji Seon;Lee, Seung-Ah;Lee, Dong-Sup;Park, Kyong Soo;Chung, Sung Soo
    • Molecules and Cells
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    • v.44 no.9
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    • pp.637-646
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    • 2021
  • Free fatty acids are converted to acyl-CoA by long-chain acyl-CoA synthetases (ACSLs) before entering into metabolic pathways for lipid biosynthesis or degradation. ACSL family members have highly conserved amino acid sequences except for their N-terminal regions. Several reports have shown that ACSL1, among the ACSLs, is located in mitochondria and mainly leads fatty acids to the β-oxidation pathway in various cell types. In this study, we investigated how ACSL1 was localized in mitochondria and whether ACSL1 overexpression affected fatty acid oxidation (FAO) rates in C2C12 myotubes. We generated an ACSL1 mutant in which the N-terminal 100 amino acids were deleted and compared its localization and function with those of the ACSL1 wild type. We found that ACSL1 adjoined the outer membrane of mitochondria through interaction of its N-terminal region with carnitine palmitoyltransferase-1b (CPT1b) in C2C12 myotubes. In addition, overexpressed ACSL1, but not the ACSL1 mutant, increased FAO, and ameliorated palmitate-induced insulin resistance in C2C12 myotubes. These results suggested that targeting of ACSL1 to mitochondria is essential in increasing FAO in myotubes, which can reduce insulin resistance in obesity and related metabolic disorders.

Regulation of glucose and glutamine metabolism to overcome cisplatin resistance in intrahepatic cholangiocarcinoma

  • So Mi Yang;Jueun Kim;Ji-Yeon Lee;Jung-Shin Lee;Ji Min Lee
    • BMB Reports
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    • v.56 no.11
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    • pp.600-605
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    • 2023
  • Intrahepatic cholangiocarcinoma (ICC) is a bile duct cancer and a rare malignant tumor with a poor prognosis owing to the lack of an early diagnosis and resistance to conventional chemotherapy. A combination of gemcitabine and cisplatin is the typically attempted first-line treatment approach. However, the underlying mechanism of resistance to chemotherapy is poorly understood. We addressed this by studying dynamics in the human ICC SCK cell line. Here, we report that the regulation of glucose and glutamine metabolism was a key factor in overcoming cisplatin resistance in SCK cells. RNA sequencing analysis revealed a high enrichment cell cycle-related gene set score in cisplatin-resistant SCK (SCK-R) cells compared to parental SCK (SCK WT) cells. Cell cycle progression correlates with increased nutrient requirement and cancer proliferation or metastasis. Commonly, cancer cells are dependent upon glucose and glutamine availability for survival and proliferation. Indeed, we observed the increased expression of GLUT (glucose transporter), ASCT2 (glutamine transporter), and cancer progression markers in SCK-R cells. Thus, we inhibited enhanced metabolic reprogramming in SCK-R cells through nutrient starvation. SCK-R cells were sensitized to cisplatin, especially under glucose starvation. Glutaminase-1 (GLS1), which is a mitochondrial enzyme involved in tumorigenesis and progression in cancer cells, was upregulated in SCK-R cells. Targeting GLS1 with the GLS1 inhibitor CB-839 (telaglenastat) effectively reduced the expression of cancer progression markers. Taken together, our study results suggest that a combination of GLUT inhibition, which mimics glucose starvation, and GLS1 inhibition could be a therapeutic strategy to increase the chemosensitivity of ICC.

Effect of a Worksite-based Dietary Intervention Program for the Management of Metabolic Syndrome (대사증후군 관리를 위한 직장기반 식생활 중재 프로그램의 효과)

  • Kim, Hye Jin;Choi, Injoo;Kim, Won Gyoung;Asano, Kana;Hong, Jeongmin;Cho, Young Min;Yoon, Jihyun
    • Korean Journal of Community Nutrition
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    • v.21 no.3
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    • pp.237-246
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    • 2016
  • Objectives: To investigate the effect of a worksite-based dietary intervention program for the management of metabolic syndrome (MS) among male employees. Methods: A dietary intervention program combining individual and environmental approach was implemented targeting white-collar employees at a worksite located in Seoul for 10 weeks. Out of 104 employees having agreed to participate in the program, those having three or more out of five components of MS and having two components, including a waist circumference component were classified into "the high risk group" (n=41) and received group nutrition education and individual nutrition counseling three times each. The rest of the study subjects were considered as "the low risk group" (n=63). The food environment at the worksite, where both the high and low risk groups were exposed, was changed to promote healthy eating. Physical data including MS components were collected and a questionnaire on dietary behaviors was administered before and after the intervention. The data from the high risk group (n=17) and the low risk group (n=20), excluding the subjects ineligible for or failed to complete the study (n=67), were analyzed. The difference before and after intervention was tested for significance by Wilcoxon signed-rank tests. Results: Weight, body mass index (BMI), waist circumference, blood pressure, HDL-cholesterol, and HbA1c and the healthy dietary practice score improved significantly after intervention in the high risk group. The median number of MS components decreased significantly from 3.0 to 1.0 in the high risk group. In the low risk group, only HbA1c significantly decreased. Conclusions: The 10-week worksite-based dietary intervention program combining individual and environmental approach was found to be effective for managing MS of male employees.

Therapeutic potential of targeting kinase inhibition in patients with idiopathic pulmonary fibrosis

  • Kim, Suji;Lim, Jae Hyang;Woo, Chang-Hoon
    • Journal of Yeungnam Medical Science
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    • v.37 no.4
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    • pp.269-276
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    • 2020
  • Fibrosis is characterized by excessive accumulation of extracellular matrix components. The fibrotic process ultimately leads to organ dysfunction and failure in chronic inflammatory and metabolic diseases such as pulmonary fibrosis, advanced kidney disease, and liver cirrhosis. Idiopathic pulmonary fibrosis (IPF) is a common form of progressive and chronic interstitial lung disease of unknown etiology. Pathophysiologically, the parenchyma of the lung alveoli, interstitium, and capillary endothelium becomes scarred and stiff, which makes breathing difficult because the lungs have to work harder to transfer oxygen and carbon dioxide between the alveolar space and bloodstream. The transforming growth factor beta (TGF-β) signaling pathway plays an important role in the pathogenesis of pulmonary fibrosis and scarring of the lung tissue. Recent clinical trials focused on the development of pharmacological agents that either directly or indirectly target kinases for the treatment of IPF. Therefore, to develop therapeutic targets for pulmonary fibrosis, it is essential to understand the key factors involved in the pathogenesis of pulmonary fibrosis and the underlying signaling pathway. The objective of this review is to discuss the role of kinase signaling cascades in the regulation of either TGF-β-dependent or other signaling pathways, including Rho-associated coiled-coil kinase, c-jun N-terminal kinase, extracellular signal-regulated kinase 5, and p90 ribosomal S6 kinase pathways, and potential therapeutic targets in IPF.

Kisspeptins (KiSS-1): Essential Players in Suppressing Tumor Metastasis

  • Prabhu, Venugopal Vinod;Sakthivel, Kunnathur Murugesan;Guruvayoorappan, Chandrasekharan
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.11
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    • pp.6215-6220
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    • 2013
  • Kisspeptins (KPs) encoded by the KiSS-1 gene are C-terminally amidated peptide products, including KP-10, KP-13, KP-14 and KP-54, which are endogenous agonists for the G-protein coupled receptor-54 (GPR54). Functional analyses have demonstrated fundamental roles of KiSS-1 in whole body homeostasis including sexual differentiation of brain, action on sex steroids and metabolic regulation of fertility essential for human puberty and maintenance of adult reproduction. In addition, intensive recent investigations have provided substantial evidence suggesting roles of Kisspeptin signalling via its receptor GPR54 in the suppression of metastasis with a variety of cancers. The present review highlights the latest studies regarding the role of Kisspeptins and the KiSS-1 gene in tumor progression and also suggests targeting the KiSS-1/GPR54 system may represent a novel therapeutic approach for cancers. Further investigations are essential to elucidate the complex pathways regulated by the Kisspeptins and how these pathways might be involved in the suppression of metastasis across a range of cancers.

Proteins as the molecular markers of male fertility

  • Beeram, Eswari
    • The Korean Journal of Food & Health Convergence
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    • v.4 no.4
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    • pp.18-25
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    • 2018
  • Proteins play a key role in many functions such as metabolic activity, differentiation, as cargos and cell fate regulators. It is necessary to know about the markers involved in male fertility in order to develop remedies for the treatment of male infertility. But, the role of the proteins is not limited to particular function in the biological systems. Some of the proteins act as ion channels such as catsper and proteins like Nanos acts as a translational repressor in germ cells and expressed in prenatal period whose role in male fertility is uncertain. Rbm5 is a pre mRNA splicing factor necessary for sperm differentiation whose loss of function results deficit in sperm production. DEFB114 is a beta defensin family protein necessary for sperm motility in LPS challenged mice where as TEX 101 is a plasma membrane specific germ cell protein whose function is not clearly known u to now. Gpr56 is another adhesion protein whose null mutation leads to arrest of production of pups in rats. Amyloid precursor protein role in Alzheimer's disease is already known but it plays an important role in male fertility also but its function is uncertain and has to be considered while targeting APP during the treatment of Alzheimer's disease. The study on amyloid precursor protein in male fertility is a novel thing but requires further study in correlation to alzheimer's disease.

Comparison of Normal Weight vs Obese Children in Terms of Family Factors, Eating Habits and Sociocognitive Factors (정상체중군과 비만군 아동의 가족요인과 식습관, 사회인지적 요인 비교)

  • Kim Hyeon Ah
    • Child Health Nursing Research
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    • v.10 no.3
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    • pp.300-310
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    • 2004
  • Purpose: To compare normal weight children with obese children in terms of family factors, eating habits, and sociocognitive factors. Method: This study compared 217 obese children with 231 normal standard weight children of 4th-6th graders from 7 elementary schools in Kangwon province. The study also surveyed 817 their parents using questionnaires in which familial factors, eating habits, and sociocognitive factors such as dietary self-efficacy, locus of control and self-esteem were included. Result: Obese children had more obese family members, more family members with chronic metabolic disease, and lower breast-feeding rate than normal weight group. Dietary self-efficacy was positively correlated with eating habits and locus of control while no correlation was found with obesity index.. Self-esteem was negatively correlate with obesity index. Both the parents and the childrens eating habits showed significant positive correlation to the obesity index. Conclusion: These results implied familial factors, eating habits, and sociocognitive factors influenced childhood obesity. Thus, further research targeting to positive attitude toward familial dietary practices combined with significant sociocognitive factors, may lead to prevention and effective management of childhood obesity.

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Trends and Perspectives in the Development of Antidiabetic Drugs for Type 2 Diabetes Mellitus (제 2형 당뇨병 치료제의 개발 동향)

  • Lee, Soo-Hyun;Lee, Jong-Keun;Kim, Ik-Hwan
    • Microbiology and Biotechnology Letters
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    • v.40 no.3
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    • pp.180-185
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    • 2012
  • Type 2 Diabetes Mellitus, a chronic metabolic disorder which results from a high blood glucose level, is one of the most prevalent and costly diseases of our time. Considering increasing rates of obesity and the aging population in Korea, the number of diabetic patients is likely to rise rapidly in the future. There are five conventional diabetic drugs which work through different mechanisms; sulfonylureas, biguanide, meglitinide, alpha-glucosidase inhibitors, and thiazolidinedione. Although they all have antidiabetic effects, some side effects such as hypoglycemia, weight gain and gastrointestinal intolerance are associated with them. Incretin based therapies, utilizing glucagon-like peptide-1 (GLP-1) and dipeptidyl peptidase-4 (DPP-4) inhibitors, which have a lower risk of adverse side effects, have recently been introduced. At present PPAR-targeting drugs are being actively developed. In this research review, particular emphasis has been placed on the current trends and possible biological targets for the new generation of antidiabetic drugs.