• BMB Reports
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• v.56 no.4
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• pp.246-251
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• 2023

Obesity increases the risk of mortality and morbidity because it results in hypertension, heart disease, and type 2 diabetes. Therefore, there is an urgent need for pharmacotherapeutic drugs to treat obesity. We performed a screening assay using natural products with anti-adipogenic properties in 3T3-L1 cells and determined that tschimganidine, a terpenoid from the Umbelliferae family, inhibited adipogenesis. To evaluate the anti-obesity effects of tschimganidine in vivo. Mice were fed either a normal chow diet (NFD) or a high-fat chow diet (HFD) with or without tschimganidine for 12 weeks. Treatment with tschimganidine decreased lipid accumulation and adipogenesis, accompanied by reduced expression of adipogenesis and lipid accumulation-related factors. Tschimganidine significantly increased the phosphorylation of AMP-activated protein kinase (AMPK) and decreased that of AKT. Depletion of AMPK relieved the reduction in lipid accumulation resulting from tschimganidine treatment. Moreover, tschimganidine administration drastically reduced the weight and size of both gonadal white adipose tissue (WAT) and blood glucose levels in high-fat diet-induced obese mice. We suggest that tschimganidine is a potent anti-obesity agent, which impedes adipogenesis and improves glucose homeostasis. Tschimganidine can then be evaluated for clinical application as a therapeutic agent.

• Molecules and Cells
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• v.41 no.10
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• pp.909-916
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• 2018

In pancreatic ${\beta}$ cells, glucose stimulates the biosynthesis of insulin at transcriptional and post-transcriptional levels. The RNA-binding protein, polypyrimidine tract-binding protein 1 (PTBP1), also named hnRNP I, acts as a critical mediator of insulin biosynthesis through binding to the pyrimidine-rich region in the 3'-untranslated region (UTR) of insulin mRNA. However, the underlying mechanism that regulates its expression in ${\beta}$ cells is unclear. Here, we report that glucose induces the expression of PTBP1 via the insulin receptor (IR) signaling pathway in ${\beta}$ cells. PTBP1 is present in ${\beta}$ cells of both mouse and monkey, where its levels are increased by glucose and insulin, but not by insulin-like growth factor 1. PTBP1 levels in immortalized ${\beta}$ cells established from wild-type (${\beta}IRWT$) mice are higher than levels in ${\beta}$ cells established from IR-null (${\beta}IRKO$) mice, and ectopic re-expression of IR-WT in ${\beta}IRKO$ cells restored PTBP1 levels. However, PTBP1 levels were not altered in ${\beta}IRKO$ cells transfected with IR-3YA, in which the Tyr1158/1162/1163 residues are substituted with Ala. Consistently, treatment with glucose or insulin elevated PTBP1 levels in ${\beta}IRWT$ cells, but not in ${\beta}IRKO$ cells. In addition, silencing Akt significantly lowered PTBP1 levels. Thus, our results identify insulin as a pivotal mediator of glucose-induced PTBP1 expression in pancreatic ${\beta}$ cells.

• Korean Journal of Agricultural Science
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• v.45 no.4
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• pp.707-713
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• 2018

This study was done to search for positional candidate genes associated with the back fat thickness trait using a Genome-Wide Association Study (GWAS) in purebred Yorkshires (N = 1755). Genotype and phenotype analyses were done for 1,642 samples. As a result of the associations with back fat thickness using the Gemma program (ver. 0.93), when the genome-wide suggestive threshold was determined using the Bonferroni method ($p=1.61{\times}10^{-5}$), the single nucleotide polymorphism (SNP) markers with suggestive significance were identified in 1 SNP marker on chromosome 2 (MARC0053928; $p=3.65{\times}10^{-6}$), 2 SNP markers on chromosome 14 (ALGA0083078; $p=7.85{\times}10^{-6}$, INRA0048453; $p=1.27{\times}10^{-5}$), and 1 SNP marker on chromosome 18 (ALGA0120564; $p=1.44{\times}10^{-5}$). We could select positional candidate genes (KCNQ1, DOCK1, LOC106506151, and LOC110257583), located close to the SNP markers. Among these, we identified a potassium voltage-gated channel subfamily Q member gene (KCNQ1) and the dedicator of cytokinesis 1 (DOCK1) gene associated with obesity and Type-2 diabetes. The SNPs and haplotypes of the KCNQ1 and DOCK1 genes can contribute to understanding the genetic structure of back fat thickness. Additionally, it may provide basic data regarding marker assisted selection for a meat quality trait in pigs.

• The Journal of Internal Korean Medicine
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• v.35 no.1
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• pp.70-78
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• 2014

Objectives : Hoechunyanggyeok-san (HYS) is a traditional herbal medicine, which has been clinically used for treating febrile and inflammatory diseases. HYS has been reported to be a useful treatment for diabetes, atherosclerosis and hyperlipidemia in the type 1 diabetic model. However, the mechanism of the effects of HYS against hyperglycemia and hyperlipidemia is poorly understood. In the present study, we investigated the underlying mechanism of ameliorative effect of HYS on hyperglycemia and hyperlipidemia in vivo. Methods : HYS (10, 50 mg/kg/day, p.o.) was administered every day for 2 weeks to db/db mice and its effect was compared with vehicle-treated db/db mice. To confirm serum glucose and triglyceride (TG) changes, serological testing was performed. The levels of sterol regulatory element-binding protein-1 (SREBP-1) activity and Sirtuin1 (SIRT1), AMP-activated protein kinase (AMPK), and acetyl-CoA carboxylase ${\alpha}$ ($ACC{\alpha}$) expression were analyzed by western blot analysis. Results : The administration of HYS significantly decreased the elevated serum glucose and TG in db/db mice. HYS administration increased the levels of SIRT1 and AMPK expression compared with the vehicle-treated group. Moreover, HYS treatment significantly inhibited SREBP-1 activity and $ACC{\alpha}$ expression in the liver, while the vehicle-treated group exhibited their increase. Conclusions : In conclusion, HYS is suggested to have an improvement effect on hyperglycemia and hyperlipidemia by activating the SIRT1/AMPK signaling pathway and inhibiting SREBP-1.

• Archives of Obesity and Metabolism
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• v.1 no.1
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• pp.4-13
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• 2022

Currently, pharmacotherapy is becoming essential for obesity, owing to its expanding and increasing epidemiology. In this review, novel peptide-based drugs of four classes are covered: GLP-1 receptor agonist, GIP/GLP-1 receptor dual agonist, glucagon/GLP-1 receptor dual agonist, and a combination of amylin receptor agonist/GLP-1 receptor agonist. Semaglutide is a next-generation GLP-1 receptor agonist with a longer duration and stronger weight and glucose reduction effects than liraglutide and dulaglutide. In the STEP1 trial, semaglutide 2.4 mg reduced body weight by approximately 15% in people with obesity with similar or milder adverse events than liraglutide 3.0 mg. Tirzepatide, a GIP/GLP-1 receptor dual agonist, also has a long duration and strong weight- and glucose-lowering effect. According to SURPASS-2, 3, and 4, in patients with BMI≥25 kg/m² and type 2 diabetes mellitus (T2DM), tirzepatide 15 mg reduced the initial body weight by >13%. Cotadutide, a glucagon/GLP-1 receptor dual agonist, showed weaker weight-lowering effects than semaglutide and tirzepatide, while it was comparable to that of liraglutide in a phase 2 clinical trial for non-alcoholic fatty liver disease in patients with BMI≥25 kg/m² and T2DM. Additionally, its effect on the liver was noticeable. The long-acting amylin receptor agonist cargrilintide combined with semaglutide can be another effective option for obesity treatment. Even in a small phase 1 trial with a short study period of 20 weeks, cargrilintide 2.4 mg/semaglutide 2.4 mg reduced by 17% of initial body weight in people with BMI 27-39.9 kg/m². In coming several years, semaglutide, tirzepatide, and cargrilintide/semaglutide will become available for obesity treatment in Korea.

• Nutrition Research and Practice
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• v.14 no.5
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• pp.519-531
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• 2020

BACKGROUND/OBJECTIVES: Regional disparities in dietary factors might be related to regional disparities in cardiometabolic health. Therefore, this study investigated the associations of cardiometabolic risk factors and dietary factors with regional types in Korean adults. SUBJECTS/METHODS: Based on data from the 2007-2017 Korea National Health and Nutrition Examination Survey, the study included 39,781 adults aged ≥ 19 years who completed the dietary survey and a health examination. Healthy and unhealthy dietary factors (fat, sodium, fruit, and vegetable intakes) were evaluated using 1-day 24-h dietary recall method, as well as the use of nutrition labels with a questionnaire. RESULTS: Of the participants, 48.7%, 36.0%, and 15.2% lived in metropolitan, urban, and rural areas, respectively. Adults living in urban and rural had higher odds ratios (ORs) for obesity (OR for urban, 1.07; 95% confidence interval (CI), 1.01-1.14; OR for rural, 1.14; 95% CI, 1.05-1.24) than adults living in metropolitan areas; these associations were significantly observed in middle-aged adults. Compared to metropolitan residents, rural residents had lower ORs for hypertension in middle-aged (OR, 0.86; 95% CI, 0.76-0.96) and metabolic syndrome in older adults (OR, 0.78; 95% CI, 0.67-0.91). Regarding urban residents, a lower OR for diabetes in middle-aged adults (OR, 0.85; 95% CI, 0.74-0.97) and a higher OR for hypertension in older adults (OR, 1.19; 95% CI, 1.02-1.39) were observed. Overall rural residents had higher ORs of excessive carbohydrate, low fruit, and high salted-vegetable intakes than metropolitan residents. Low fruit intake was positively associated with obesity, metabolic syndrome, and hypertension, after adjustment for regional type and other confounders in total participants. CONCLUSIONS: These findings indicate that cardiometabolic risk and unhealthy dietary factors differ among regional types and age groups within Korea. Nutritional policy and interventions should consider regional types for prevention and management of cardiometabolic risk factors.

• The Korea Journal of Herbology
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• v.28 no.4
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• pp.49-55
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• 2013

Objectives : Mori Folium was popularly used as one of the traditional medicinal herbs. Although M. Folium has been cultivated for rearing silkworm historically, it's use has been expanded as natural therapeutic agent for the treatment of filariasis, diabetes and dropsy in East Asia. However, little has been known about the effect of M. Folium on liver fibrosis. Therefore, we would like to explore an anti-fibrogenic potential of M. Folium extract (MFE) using immortalized human hepatic stellate cell line, LX-2 cells. Methods : We examined the effects of MFE on the transforming growth factor ${\beta}1$ ($TGF{\beta}1$)-induced liver fibrosis in LX-2 cells. Cell viability, Smad binding element-driven luciferase activity, phosphorylations level of Smad 2/3, and expression level of $TGF{\beta}1$-dependent target genes were monitored in the MFE-treated LX-2 cells. Results : Up to 30 ${\mu}g/ml$ MFE treatment did not show any possible toxic effect in LX-2 cells. MFE inhibited $TGF{\beta}1$-inducible Smad binding element-driven luciferase activity and decreased the $TGF{\beta}1$-inducible phosphorylations of Smad 2 and Smad 3 in hepatic stellate cell in a dose dependent manner. Furthermore, increases of plasminogen activator inhibitor type 1, $TGF{\beta}1$ and matrix metalloproteinases 2 genes by $TGF{\beta}1$ were also attenuated by MFE treatment. Conclusions : These findings suggested that MFE would be used as a potential therapeutic agent for the treatment liver fibrosis, which might be mediated by the inhibition of $TGF{\beta}1$-inducible Smad 2/3 transactivation and target genes expression.

• Health Policy and Management
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• v.19 no.3
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• pp.92-108
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• 2009

This study suggests a model for continuing and comprehensive management of hypertension or Type 2 diabetes mellitus (T2DM) in Korea. Moreover, this paper computed the contribution cost of hypertension or T2DM management using the healthcare medical cost, which could have occurred from stroke, myocardial infarction (MI), and end-stage renal disease (ESRD) that were successfully prevented from the effective hypertension or T2DM management. Additionally, these costs were compared with the cost of implementing the hypertension or T2DM management model suggested in this study. This study used the medical fee summary of the health insurance claims submitted to National Health Insurance Corporation by medical facilities for services provided during the period from January 1st 1999 to December 31st 2006. The prevalence rate with treatment referred to cases in which patients submitted their medical claims at least once during the period, along with an accordant diagnosis. The incidence rate with treatment referred to cases in which patients who never submitted claims for the accordant disease during the five years from 1999 to 2003 submitted claims for the accordant disease in 2004 and 2005. The relative risk of the occurrence of stroke, MI and ESRD was 11.0, 13.6, and 30.3, respectively. The attributable risk of hypertension or T2DM for stroke was 0.730, and that for MI and ESRD were 0.773 and 0.888, respectively. Based on these, the contribution cost of hypertension or T2DM is estimated to be 986.3 billion Korean Won(KRW) for stroke patients, 330.5 billion KRW for MI patients, and 561.7 billion KRW for ESRD patients as in 2005. Hence, the total contribution cost of hypertension or T2DM to stroke, MI, and ESRD is 1.878 trillion KRW. The estimate for operational costs included an annual expenditure of 50,000 KRW per each recipient and an annual subsidy of 0.22 million KRW per person for the 1.6 million low.income individuals with hypertension or T2DM to cover their out.of.pocket medical expenses. Under this assumption, it took approximately 0.6 trillion KRW to manage 5 million high.risk patients in the low. and mid.income range, coverings up to 50% of costs. In conclusion, considering the potential benefits of preventing stroke, MI, and ESRD, the costs seems to be reasonable.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.5
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• pp.519-529
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• 2017

Sodium butyrate (SB) has various metabolic actions. However, its effect on dipeptidyl peptidase 4 (DPP-4) needs to be studied further. We aimed to evaluate the metabolic actions of SB, considering its physiologically relevant concentration. We evaluated the effect of SB on regulation of DPP-4 and its other metabolic actions, both in vitro (HepG2 cells and mouse mesangial cells) and in vivo (high fat diet [HFD]-induced obese mice). Ten-week HFD-induced obese C57BL/6J mice were subjected to SB treatment by adding SB to HFD which was maintained for an additional 16 weeks. In HepG2 cells, SB suppressed DPP-4 activity and expression at sub-molar concentrations, whereas it increased DPP-4 activity at a concentration of $1,000{\mu}M$. In HFD-induced obese mice, SB decreased blood glucose, serum levels of insulin and $IL-1{\beta}$, and DPP-4 activity, and suppressed the increase in body weight. On the contrary, various tissues including liver, kidney, and peripheral blood cells showed variable responses of DPP-4 to SB. Especially in the kidney, although DPP-4 activity was decreased by SB in HFD-induced obese mice, it caused an increase in mRNA expression of $TNF-{\alpha}$, IL-6, and $IL-1{\beta}$. The pro-inflammatory actions of SB in the kidney of HFD-induced obese mice were recapitulated by cultured mesangial cell experiments, in which SB stimulated the secretion of several cytokines from cells. Our results showed that SB has differential actions according to its treatment dose and the type of cells and tissues. Thus, further studies are required to evaluate its therapeutic relevance in metabolic diseases including diabetes and obesity.

• Journal of Nutrition and Health
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• v.56 no.1
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• pp.24-34
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• 2023

Purpose: The prevalence of diabetes mellitus (DM) continues to increase worldwide, and blood glucose control may reduce mortality from diabetic complications and healthcare costs. Mulberry twig (MT) has been used as a herbal medicine in Asia, and its antidiabetic efficacy has recently been reported, but research in this area is still limited. This study examined the antidiabetic effects of water extracts of MT in diabetic animals. Methods: Six weeks old male ICR mice were divided randomly into three groups; normal control (NC, n = 10), DM control (DC, n = 10), and MT (n = 10). Streptozotocin (STZ, 50 mg/kg/day) was injected intraperitoneally into mice in the DC and MT groups for 5 consecutive days. After 10 days of the last STZ injection, the mice in the MT group were administered orally with MT water extracts (5 g/kg body weight) for 16 days. Results: The MT water extracts ameliorated the swelling of the liver in the diabetic mice and reduced the elevated levels of fasting blood and plasma glucose, total cholesterol (T-CHO), low density lipoprotein-CHO, and the ratio of high density lipotrotein (HDL)-CHO/T-CHO. The liver triglyceride (TG) and glycogen contents were also significantly lower in the MT group mice than in the DC group. The small intestine disaccharidase activity was analyzed to understand the therapeutic effects and the mechanism of MT water extracts in diabetic animals. MT group mice showed reduced lactase and sucrase activity in the proximal part of the small intestine. On the other hand, body weight, plasma insulin, TG, HDL-CHO, and hepatic T-CHO levels were similar in the DC and MT groups. Conclusion: These results suggest that MT water extracts have antidiabetic effects and can be developed as a functional source to reduce the postprandial blood glucose or to prevent DM incidence.