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Ji Young Lee  (Lee JY) 3 Articles
Basic Research
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Ipragliflozin, an SGLT2 Inhibitor, Ameliorates High-Fat Diet-Induced Metabolic Changes by Upregulating Energy Expenditure through Activation of the AMPK/ SIRT1 Pathway
Ji-Yeon Lee, Minyoung Lee, Ji Young Lee, Jaehyun Bae, Eugene Shin, Yong-ho Lee, Byung-Wan Lee, Eun Seok Kang, Bong-Soo Cha
Diabetes Metab J. 2021;45(6):921-932.   Published online February 22, 2021
DOI: https://doi.org/10.4093/dmj.2020.0187
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  • 434 Download
  • 21 Web of Science
  • 22 Crossref
Graphical AbstractGraphical Abstract AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Sodium-glucose co-transporter 2 (SGLT2) inhibitors are a new class of antidiabetic drugs that exhibit multiple extraglycemic effects. However, there are conflicting results regarding the effects of SGLT2 inhibition on energy expenditure and thermogenesis. Therefore, we investigated the effect of ipragliflozin (a selective SGLT2 inhibitor) on energy metabolism.
Methods
Six-week-old male 129S6/Sv mice with a high propensity for adipose tissue browning were randomly assigned to three groups: normal chow control, 60% high-fat diet (HFD)-fed control, and 60% HFD-fed ipragliflozin-treated groups. The administration of diet and medication was continued for 16 weeks.
Results
The HFD-fed mice became obese and developed hepatic steatosis and adipose tissue hypertrophy, but their random glucose levels were within the normal ranges; these features are similar to the metabolic features of a prediabetic condition. Ipragliflozin treatment markedly attenuated HFD-induced hepatic steatosis and reduced the size of hypertrophied adipocytes to that of smaller adipocytes. In the ipragliflozin treatment group, uncoupling protein 1 (Ucp1) and other thermogenesis-related genes were significantly upregulated in the visceral and subcutaneous adipose tissue, and fatty acid oxidation was increased in the brown adipose tissue. These effects were associated with a significant reduction in the insulin-to-glucagon ratio and the activation of the AMP-activated protein kinase (AMPK)/sirtuin 1 (SIRT1) pathway in the liver and adipose tissue.
Conclusion
SGLT2 inhibition by ipragliflozin showed beneficial metabolic effects in 129S6/Sv mice with HFD-induced obesity that mimics prediabetic conditions. Our data suggest that SGLT2 inhibitors, through their upregulation of energy expenditure, may have therapeutic potential in prediabetic obesity.

Citations

Citations to this article as recorded by  
  • SGLT2 inhibitors and AMPK: The road to cellular housekeeping?
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    Clinical Kidney Journal.2024;[Epub]     CrossRef
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    Clinics in Liver Disease.2023; 27(2): 397.     CrossRef
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    Panagiotis Theofilis, Rigas G. Kalaitzidis
    Current Medicinal Chemistry.2023; 30(23): 2595.     CrossRef
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    Frontiers in Pharmacology.2023;[Epub]     CrossRef
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    Ema Schönberger, Vjera Mihaljević, Kristina Steiner, Sandra Šarić, Tomislav Kurevija, Ljiljana Trtica Majnarić, Ines Bilić Ćurčić, Silvija Canecki-Varžić
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    Renal Failure.2023;[Epub]     CrossRef
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    Cardiovascular Diabetology.2023;[Epub]     CrossRef
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    Ke Lin, Na Yang, Wu Luo, Jin-fu Qian, Wei-wei Zhu, Shi-ju Ye, Chen-xin Yuan, Di-yun Xu, Guang Liang, Wei-jian Huang, Pei-ren Shan
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    Panagiotis Theofilis, Marios Sagris, Evangelos Oikonomou, Alexios S. Antonopoulos, Gerasimos Siasos, Kostas Tsioufis, Dimitris Tousoulis
    Diabetes Research and Clinical Practice.2022; 188: 109927.     CrossRef
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    Sandra Feijóo-Bandín, Alana Aragón-Herrera, Manuel Otero-Santiago, Laura Anido-Varela, Sandra Moraña-Fernández, Estefanía Tarazón, Esther Roselló-Lletí, Manuel Portolés, Oreste Gualillo, José Ramón González-Juanatey, Francisca Lago
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  • Potential molecular mechanism of action of sodium-glucose co-transporter 2 inhibitors in the prevention and management of diabetic retinopathy
    Lia Meuthia Zaini, Arief S Kartasasmita, Tjahjono D Gondhowiardjo, Maimun Syukri, Ronny Lesmana
    Expert Review of Ophthalmology.2022; 17(3): 199.     CrossRef
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    Juexing Li, Lei Zhou, Hui Gong
    Frontiers in Cardiovascular Medicine.2022;[Epub]     CrossRef
  • Critical Reanalysis of the Mechanisms Underlying the Cardiorenal Benefits of SGLT2 Inhibitors and Reaffirmation of the Nutrient Deprivation Signaling/Autophagy Hypothesis
    Milton Packer
    Circulation.2022; 146(18): 1383.     CrossRef
  • Nutraceutical activation of Sirt1: a review
    James J DiNicolantonio, Mark F McCarty, James H O'Keefe
    Open Heart.2022; 9(2): e002171.     CrossRef
  • Dapagliflozin Restores Impaired Autophagy and Suppresses Inflammation in High Glucose-Treated HK-2 Cells
    Jing Xu, Munehiro Kitada, Yoshio Ogura, Haijie Liu, Daisuke Koya
    Cells.2021; 10(6): 1457.     CrossRef
  • Could Sodium/Glucose Co-Transporter-2 Inhibitors Have Antiarrhythmic Potential in Atrial Fibrillation? Literature Review and Future Considerations
    Dimitrios A. Vrachatis, Konstantinos A. Papathanasiou, Konstantinos E. Iliodromitis, Sotiria G. Giotaki, Charalampos Kossyvakis, Konstantinos Raisakis, Andreas Kaoukis, Vaia Lambadiari, Dimitrios Avramides, Bernhard Reimers, Giulio G. Stefanini, Michael C
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  • Differential Pathophysiological Mechanisms in Heart Failure With a Reduced or Preserved Ejection Fraction in Diabetes
    Milton Packer
    JACC: Heart Failure.2021; 9(8): 535.     CrossRef
  • Ketone bodies: from enemy to friend and guardian angel
    Hubert Kolb, Kerstin Kempf, Martin Röhling, Martina Lenzen-Schulte, Nanette C. Schloot, Stephan Martin
    BMC Medicine.2021;[Epub]     CrossRef
Balsamic Vinegar Improves High Fat-Induced Beta Cell Dysfunction via Beta Cell ABCA1
Hannah Seok, Ji Young Lee, Eun Mi Park, Se Eun Park, Jae Hyuk Lee, Seungtaek Lim, Byung-Wan Lee, Eun Seok Kang, Hyun Chul Lee, Bong Soo Cha
Diabetes Metab J. 2012;36(4):275-279.   Published online August 20, 2012
DOI: https://doi.org/10.4093/dmj.2012.36.4.275
  • 5,226 View
  • 52 Download
  • 10 Crossref
AbstractAbstract PDFPubReader   
Background

The aim of this study was to investigate the effects of balsamic vinegar on β-cell dysfunction.

Methods

In this study, 28-week-old Otsuka Long-Evans Tokushima Fatty (OLETF) rats were fed a normal chow diet or a high-fat diet (HFD) and were provided with tap water or dilute balsamic vinegar for 4 weeks. Oral glucose tolerance tests and histopathological analyses were performed thereafter.

Results

In rats fed both the both chow diet and the HFD, the rats given balsamic vinegar showed increased insulin staining in islets compared with tap water administered rats. Balsamic vinegar administration also increased β-cell ATP-binding cassette transporter subfamily A member 1 (ABCA1) expression in islets and decreased cholesterol levels.

Conclusion

These findings provide the first evidence for an anti-diabetic effect of balsamic vinegar through improvement of β-cell function via increasing β-cell ABCA1 expression.

Citations

Citations to this article as recorded by  
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Dietary Oleate Has Beneficial Effects on Every Step of Non-Alcoholic Fatty Liver Disease Progression in a Methionine- and Choline-Deficient Diet-Fed Animal Model
Ji Young Lee, Jae Hoon Moon, Jong Suk Park, Byung-Wan Lee, Eun Seok Kang, Chul Woo Ahn, Hyun Chul Lee, Bong Soo Cha
Diabetes Metab J. 2011;35(5):489-496.   Published online October 31, 2011
DOI: https://doi.org/10.4093/dmj.2011.35.5.489
  • 30,999 View
  • 47 Download
  • 17 Crossref
AbstractAbstract PDFPubReader   
Background

Non-alcoholic fatty liver disease (NAFLD) is increasingly recognized as a major cause of liver-related morbidity and mortality. The underlying mechanisms of disease progression remain poorly understood, and primary therapy of NAFLD is not yet established. We investigated the effects of dietary oleate on the development and progression of NAFLD in a methionine- and choline-deficient (MCD) diet-fed animal model.

Methods

A total of 30 C57BL/6J mice were randomly divided into three groups (n=10 in each group) and fed various experimental diets for four weeks: chow, MCD diet, or OMCD (MCD diet with oleate, 0.5 mg/g/day). Liver samples were examined for steatohepatitis and fibrosis parameters and associated genes.

Results

Additional dietary oleate dramatically reduced MCD diet-induced hepatic steatosis. Hepatic carbohydrate responsive element-binding protein was overexpressed in MCD diet-fed mice, and dietary oleate prevented this overexpression (P<0.001). Dietary oleate partially prevented MCD diet-induced serum level increases in aspartate aminotransferase and alanine aminotransferase (P<0.001, respectively). The mRNA expressions of hepatic monocyte chemoattractant protein 1, tumor necrosis factor-α and matrix metalloproteinase-9 were increased in MCD diet-fed mice, and this overexpression of inflammatory molecules was prevented by dietary oleate (P<0.001). Hepatic pericellular fibrosis was observed in MCD diet-fed mice, and dietary oleate prevented this fibrosis. Altogether, dietary oleate prevented MCD diet-induced hepatic steatosis, inflammation and fibrosis.

Conclusion

Dietary oleate has beneficial effects in every step of NAFLD development and progression and could be a nutritional option for NAFLD prevention and treatment.

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