Endocrinology and Metabolism

Original Articles

Diabetes, obesity and metabolism
Phloretin Ameliorates Succinate-Induced Liver Fibrosis by Regulating Hepatic Stellate Cells: Cong Thuc Le, Giang Nguyen, So Young Park, Hanh Nguyen Dong, Yun Kyung Cho, Jae-Ho Lee, Seung-Soon Im, Dae-Hee Choi, Eun-Hee Cho; Endocrinol Metab. 2023;38(4):395-405. Published online August 3, 2023; DOI: https://doi.org/10.3803/EnM.2023.1661

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Abstract PDF PubReader ePub: Background
Hepatic stellate cells (HSCs) are the major cells which play a pivotal role in liver fibrosis. During injury, extracellular stimulators can induce HSCs transdifferentiated into active form. Phloretin showed its ability to protect the liver from injury, so in this research we would like to investigate the effect of phloretin on succinate-induced HSCs activation in vitro and liver fibrosis in vivo study.
Methods
In in vitro, succinate was used to induce HSCs activation, and then the effect of phloretin on activated HSCs was examined. In in vivo, succinate was used to generated liver fibrosis in mouse and phloretin co-treated to check its protection on the liver.
Results
Phloretin can reduce the increase of fibrogenic markers and inhibits the proliferation, migration, and contraction caused by succinate in in vitro experiments. Moreover, an upregulation of proteins associated with aerobic glycolysis occurred during the activation of HSCs, which was attenuated by phloretin treatment. In in vivo experiments, intraperitoneal injection of phloretin decreased expression of fibrotic and glycolytic markers in the livers of mice with sodium succinate diet-induced liver fibrosis. These results suggest that aerobic glycolysis plays critical role in activation of HSCs and succinate can induce liver fibrosis in mice, whereas phloretin has therapeutic potential for treating hepatic fibrosis.
Conclusion
Intraperitoneal injection of phloretin attenuated succinate-induced hepatic fibrosis and alleviates the succinate-induced HSCs activation.

Diabetes, Obesity and Metabolism
Stimulation of Alpha-1-Adrenergic Receptor Ameliorates Obesity-Induced Cataracts by Activating Glycolysis and Inhibiting Cataract-Inducing Factors: Yong-Jik Lee, Yoo-Na Jang, Hyun-Min Kim, Yoon-Mi Han, Hong Seog Seo, Youngsub Eom, Jong-suk Song, Ji Hoon Jeong, Tae Woo Jung; Endocrinol Metab. 2022;37(2):221-232. Published online March 23, 2022; DOI: https://doi.org/10.3803/EnM.2021.1237

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Background
Obesity, the prevalence of which is increasing due to the lack of exercise and increased consumption of Westernized diets, induces various complications, including ophthalmic diseases. For example, obesity is involved in the onset of cataracts.
Methods
To clarify the effects and mechanisms of midodrine, an α1-adrenergic receptor agonist, in cataracts induced by obesity, we conducted various analytic experiments in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a rat model of obesity.
Results
Midodrine prevented cataract occurrence and improved lens clearance in OLETF rats. In the lenses of OLETF rats treated with midodrine, we observed lower levels of aldose reductase, tumor necrosis factor-α, and sorbitol, but higher levels of hexokinase, 5’-adenosine monophosphate-activated protein kinase-alpha, adenosine 5´-triphosphate, peroxisome proliferator-activated receptordelta, peroxisome proliferator-activated receptor gamma coactivator 1-alpha, superoxide dismutase, and catalase.
Conclusion
The ameliorating effects of midodrine on cataracts in the OLETF obesity rat model are exerted via the following three mechanisms: direct inhibition of the biosynthesis of sorbitol, which causes cataracts; reduction of reactive oxygen species and inflammation; and (3) stimulation of normal aerobic glycolysis.

Citations

Citations to this article as recorded by

α1-Adrenergic Receptors: Insights into Potential Therapeutic Opportunities for COVID-19, Heart Failure, and Alzheimer’s Disease
Dianne M. Perez
International Journal of Molecular Sciences.2023; 24(4): 4188. CrossRef
A new use for old drugs: identifying compounds with an anti-obesity effect using a high through-put semi-automated Caenorhabditis elegans screening platform
Freek Haerkens, Charlotte Kikken, Laurens Kirkels, Monique van Amstel, Willemijn Wouters, Els van Doornmalen, Christof Francke, Samantha Hughes
Heliyon.2022; 8(8): e10108. CrossRef

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