Gymnaster koraiensis extract alleviated metabolic syndrome symptoms with UCP1-independent energy expenditure in diet induced obese mice model Da Seul Jung¹,², Yang-Ju Son¹, Ji Min Shin¹, Saruul Erdenebileg¹, Chang Ho Lee², Chu Won Nho¹ ¹Smart Farm Reserch Center, Korea Institute of Science and Technology (KIST) Gangneung Institute of Natural Products, Gangneung Gangwon-do, Korea ²Biology, Gangneung-Wonju National University, Gangneung Gangwon-do, Korea Abstract & Purpose Metabolic syndrome is a medical term that represents a state of co-occurrence of more than three pathologic risk factors
like abdominal obesity, insulin resistance, hypertension, hyperglycemia, and hyperlipidemia. Metabolic syndrome can lead to serious diseases such as diabetes and cardiovascular disease, and since so far single drug used to treat each symptom, we are looking for a functional food material for anti-obesity and metabolic syndrome with multi-target effect. Gymnaster koraiensis (GK) is an edible plant of Korea known for its anti-cancer, anti-oxidative, and hepatoprotective properties. In this study, we hypothesized that the GK ethanol extract could be utilized for treating obesity and metabolic
syndrome. Administration of 100mg/kg GK extract to high-fat dietary induced obese (DIO) mice effectively reduced body weight, weight of fat tissues, and size of white adipose tissues. It also ameliorated cardiovascular disease risk by regulating hyperlipidemia and adiponectin contents. Moreover, GK extract improved insulin resistance by lowering fasting blood glucose levels, mitigating oxidative stress and inflammation. In addition, supplementation of GK extract in DIO mice resulted in elevated energy expenditure in white adipose tissue by increased mitochondrial oxidative capacity and lipid
Fig. 2 Effects of GK on anti-oxidative and inflammatory responses in DIO mice. (A) MDA content in WAT. (B) The catabolism through upregulated adenosine monophosphate-activated protein kinase expression of proteins related with anti-oxidative responses such as NQO1, HO-1, SOD1, and SOD2. (C) The IL-1β content in serum. (D) The mRNA levels of chemokine (MCP1), cytokine (IL-1β, IFNγ) and macrophage marker (CD11c, (AMPK) signaling. Thus, GK extract treatment prominently ameliorated metabolic F4/80). Different superscripts represent statistical differences at p<0.05. syndrome related symptoms like
obesity, hyperlipidemia, hyperglycemia, and insulin resistance. Hence, GK extract can be a promising multi-target functional food which can improve metabolic syndrome related symptoms. Fig. 3 Changes of OGTT, IPITT, HOMA-IR, and Akt molecular signaling by Results administration of GK in DIO mice. The OGTT and IPITT tests were conducted with mice at 7th week from the oral treatment after 6 h fasting. The blood was collected from tail vein at 0, 30, 60, 120 and 180 min. (A) The blood glucose levels measured by OGTT. (B) The AUC of OGTT. (C) The blood glucose levels measured by IPITT. (D) The AUC
of IPITT. (E) The serum insulin content. (F) The HOMA-IR graph. (G) The protein levels of Akt and p-Akt (ser473) were Table. 1 Effect of GK treatment on weight gain, food intake and serum biochemical parameters in HFD-fed mice. determined by western blot. Different superscripts represent statistical differences Different superscripts within rows represent statistical differences at p<0.05. at p<0.05. Fig 4 GK intake upregulated UCP-1 independent energy expenditure mechanisms in eWAT of DIO mice. (A) The protein expression levels of AMPK, p-AMPK, PRDM16, UCP1 and Cytochrome C in eWAT. (B) The
mRNA levels of mitochondrial biogenesis and fatty acid oxidation related markers. (C) The mRNA levels of TAG/FA cycle related markers. Different superscripts represent statistical differences at p<0.05. Conclusions 1. GK intake effectively reduced body and fat weight. 2. GK has improvement effect of hyperlipidemia and cardiovascular disease risk factor by reduced serum TG, TC and ratio of LDL-c/HDL-c. 3. GK intake ameliorated dysfunction of WAT by reduced serum leptin content and increased serum adiponectin content. 4. GK intake reduced adipocyte size by decreased adipogenesis related proteins
(PPARr, C/EBPa) and lipogenesis related proteins (SREBP-1, FAS) and increased p-AMPK, p-ACC, CPT1 proteins expression level. GK administration ameliorated oxidative stress by reduced MDA content and increased scavenger proteins such as NQO1, HO-1 and SOD2. 5. GK administration improve obesity-related inflammation by reduced serum IL-1b and mRNA levels of IL-1b, IFNr, F4/80 and CD11c. 6. GK intake suppressed insulin resistance by improved fasting glucose level (showed OGTT, IPITT results) and decreased HOMA-IR and increased p-Akt 7. GK has possibility of increased UCP1-independent energy
expenditure in eWAT by increased mitochondria biogenesis, oxidative capacity and TAG/FA cycle in lipid catabolism, which highly energy demand. Fig. 1 The tissue morphology of eWAT and adipogenic and lipid metabolism related protein expression in DIO mice with GK treatment. (A) Representative image of H&E stained section of eWAT. The magnitude was 100x and the 8. Taken together, GK extract has multi targeting effect to alleviate obesity and scale bar indicates 200 μm. The arrow in HFD image shows crown like structures. (B) Average of adipocyte size area. metabolic syndrome. Thus, we suggest
that GK can be an effective functional food (C) Adipocyte size distribution of eWAT. (D) Adipogenesis related markers (PPARγ, C/EBPα) were observed by western for attenuating obesity and metabolic syndrome. blot analysis. (E) AMPK, p-AMPK, ACC, p-ACC, lipogenesis marker (SREBP-1, FAS), and fatty acid oxidation marker (CPT1) were observed by western blot analysis. Different superscripts represent statistical differences at p<0.05. Acknowledgments This study was supported by the Korea–Mongolia Cooperation Project from the National Research Foundation of Korea (NRF) (grant number 2008-00592).
Also, this work was supported by an intramural grant from the Korea Institute of Science and Technology, Gangneung Institute (grant number 2Z05630). [N. Metabolism and metabolic diseases-1] Gymnaster koraiensis extract alleviated metabolic syndrome symptoms in diet induced obese mice Da Seul Jung¹˙², Yang-Ju Son¹, Ji Min Shin¹, Saruul Erdenebileg¹, Chang Ho Lee², Chu Won Nho¹ ¹Smart Farm Reserch Center, Korea Institute of Science and Technology (KIST) Gangneung Institute of Natural Products, Gangneung Gangwon-do, Korea, ²Biology, Gangneung-Wonju National University, Gangneung Gangwon-do, Korea
Metabolic syndrome is a medical condition that at least three of pathologic risk factors co-occurred among abdominal obesity, insulin resistance, hypertension, hyperglycemia and hyperlipidemia. Gymnaster koraiensis (GK) is known for its beneficial effects about anti-cancer, anti-oxidative stress, and protecting liver injury; but its efficacies on obesity and metabolic syndrome have not been determined yet. This study examined the effects of GK extract on obesity and metabolic syndrome in diet induced obese (DIO) mice model. Administration of GK extract to DIO mice reduced body weight and
ameliorated fasting blood glucose, obesity-related inflammation, and oxidative stress. Moreover, GK extract elevated energy expenditure in white adipose tissue by upregulating AMPK signaling. In conclusion, GK extract treatment prominently ameliorated metabolic syndrome related symptoms like obesity, hyperlipidemia, hyperglycemia, and insulin resistance. Hence, GK extract can be a promising therapeutic agent with multi-target improvement of metabolic syndrome related symptoms. Comprehensive Multi-Omics Analysis Reveals Aberrant Metabolism of Epstein–Barr-Virus-Associated Gastric Carcinoma 2 2
1 2 Jun Yeob Kim, 1,† Sang Jun Yoon, 2,† Nguyen Phuoc Long, Jung Eun Min, Hyung Min Kim, Jae Hee Yoon, Nguyen Hoang Anh, Myung Chan Park, Sung Won Kwon, 2,* and Suk Kyeong Lee 1,* 1 2 1. Department of Medical Life Sciences, Department of Biomedicine & Health Sciences, College of Medicine, The Catholic University of Korea 2. College of Pharmacy, Seoul National University I. Abstract The metabolic landscape of Epstein–Barr-virus-associated gastric cancer (EBVaGC) remains to be elucidated. We used transcriptomics, metabolomics, and lipidomics to comprehensively investigate aberrant metabolism in
EBVaGC. Specifically, we conducted gene expression analyses using microarray-based data from gastric adenocarcinoma epithelial cell lines and tissue samples from patients with clinically advanced gastric carcinoma. We also conducted complementary metabolomics and lipidomics using various mass spectrometry platforms. We found a significant downregulation of genes related to metabolic pathways, especially the metabolism of amino acids, lipids, and carbohydrates. The effect of dysregulated metabolic genes was confirmed in a survival analysis of 3951 gastric cancer patients. 15 metabolisms related
to polar metabolites and 15 lipid-associated pathways were involved in alteration of metabolites by EBV in gastric cancer. In this work, we have described the metabolic landscape of EBVaGC at the multi-omics level. These findings could help elucidate the mechanism of EBVaGC oncogenesis. II. Method Table 1. The lipid metabolic pathways derived from lipids significantly altered by EBV. III. Results Fig 1. Principal component analysis (PCA) score plots of differences in transcriptome profiles (a) between AGS-EBV and AGS and (b) gastric cancer tissue (GCT)-EBV and GCT. Fig 4. Metabolic profiles of
AGS-EBV and AGS made using GC-MS and HPLC-QqQ MS. (a) 2D score plot and (b) the heatmap derived using the untargeted GC-MS method. (c) 2D score plot and (d) the heatmap derived from the HPLC-QqQ MS method. (e) The pathway analysis based on polar metabolites differentially expressed between AGS-EBV and AGS suggests that 15 metabolic pathways are significantly (p-value < 0.05, FDR < 0.1) associated with the effect of EBV infection on gastric cancer. Fig 2. Kaplan–Meier (KM) plots show the effects of the significantly down-regulated metabolic genes found in our study. HR: hazard ratio. Fig3.
Differential expression of lipids between AGS-EBV and AGS. (a) 2D score plot and (b) the heatmap derived from the lipid profile based on the untargeted UPLC-QToF MS method. Fig 5. The metabolic landscape of EBV-associated gastric carcinoma. IV. Conclusions By using a comprehensive multi-omics approach, we established the metabolic landscape of EBVaGC and generated a comprehensive framework for mechanistic studies. The metabolic dysregulations in EBVaGC could be associated with the clinical prognosis of GC patients. Differences in lipid expression between EBVaGC and EBVnGC were notably
supported in the present study. Collectively, these findings could be used to discover and validate new biomarkers and therapeutics for EBVaGC. [N. Metabolism and metabolic diseases-2] Comprehensive multi-omics analysis reveals aberrant metabolism of Epstein-Barr-Virus-associated gastric carcinoma Jun Yeob Kim¹˙#, Sang Jun Yoon²˙#, Nguyen Phuoc Long², Jung Eun Min², Hyung Min Kim², Jae Hee Yoon¹, Nguyen Hoang Anh², Myung Chan Park¹, Sung Won Kwon²˙*, Suk Kyeong Lee¹˙* ¹Department of Medical Life Sciences, Department of Biomedicine & Health Sciences, College of Medicin, The Catholic University
of Korea, Seoul 06591, South Korea, ²College of Pharmacy, Seoul National University, Seoul 08826, South Korea The metabolic landscape of Epstein–Barr-virus-associated gastric cancer (EBVaGC) remains to be elucidated. We used transcriptomics, metabolomics, and lipidomics to comprehensively investigate aberrant metabolism in EBVaGC. Specifically, we conducted gene expression analyses using microarray-based data from gastric adenocarcinoma epithelial cell lines and tissue samples from patients with clinically advanced gastric carcinoma. We also conducted complementary metabolomics and lipidomics
using various mass spectrometry
