Diabetes & Metabolism Journal

Original Articles

Basic Research
Extracellular Vimentin Alters Energy Metabolism And Induces Adipocyte Hypertrophy: Ji-Hae Park, Soyeon Kwon, Young Mi Park; Diabetes Metab J. 2024;48(2):215-230. Published online September 26, 2023; DOI: https://doi.org/10.4093/dmj.2022.0332

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Background
Previous studies have reported that oxidative stress contributes to obesity characterized by adipocyte hypertrophy. However, mechanism has not been studied extensively. In the current study, we evaluated role of extracellular vimentin secreted by oxidized low-density lipoprotein (oxLDL) in energy metabolism in adipocytes.
Methods
We treated 3T3-L1-derived adipocytes with oxLDL and measured vimentin which was secreted in the media. We evaluated changes in uptake of glucose and free fatty acid, expression of molecules functioning in energy metabolism, synthesis of adenosine triphosphate (ATP) and lactate, markers for endoplasmic reticulum (ER) stress and autophagy in adipocytes treated with recombinant vimentin.
Results
Adipocytes secreted vimentin in response to oxLDL. Microscopic evaluation revealed that vimentin treatment induced increase in adipocyte size and increase in sizes of intracellular lipid droplets with increased intracellular triglyceride. Adipocytes treated with vimentin showed increased uptake of glucose and free fatty acid with increased expression of plasma membrane glucose transporter type 1 (GLUT1), GLUT4, and CD36. Vimentin treatment increased transcription of GLUT1 and hypoxia-inducible factor 1α (Hif-1α) but decreased GLUT4 transcription. Adipose triglyceride lipase (ATGL), peroxisome proliferator-activated receptor γ (PPARγ), sterol regulatory element-binding protein 1 (SREBP1), diacylglycerol O-acyltransferase 1 (DGAT1) and 2 were decreased by vimentin treatment. Markers for ER stress were increased and autophagy was impaired in vimentin-treated adipocytes. No change was observed in synthesis of ATP and lactate in the adipocytes treated with vimentin.
Conclusion
We concluded that extracellular vimentin regulates expression of molecules in energy metabolism and promotes adipocyte hypertrophy. Our results show that vimentin functions in the interplay between oxidative stress and metabolism, suggesting a mechanism by which adipocyte hypertrophy is induced in oxidative stress.

Citations

Citations to this article as recorded by

Novel secreted regulators of glucose and lipid metabolism in the development of metabolic diseases
Lianna W. Wat, Katrin J. Svensson
Diabetologia.2024;[Epub] CrossRef
Mechanobiology in Metabolic Dysfunction-Associated Steatotic Liver Disease and Obesity
Emily L. Rudolph, LiKang Chin
Current Issues in Molecular Biology.2024; 46(7): 7134. CrossRef
Context-specific fatty acid uptake is a finely-tuned multi-level effort
Juan Wang, Huiling Guo, Lang-Fan Zheng, Peng Li, Tong-Jin Zhao
Trends in Endocrinology & Metabolism.2024;[Epub] CrossRef
The Functions of SARS-CoV-2 Receptors in Diabetes-Related Severe COVID-19
Adam Drzymała
International Journal of Molecular Sciences.2024; 25(17): 9635. CrossRef

Effect of Oxidized LDL on Neutrophil Adhesion and Transendothelial Migration.: Seok Man Son, In Ju Kim, Yong Ki Kim; Korean Diabetes J. 1999;23(1):12-24. Published online January 1, 2001

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Abstract PDF: BACKGROUND
It is well recognized that oxidized low density lipoproteins (ox-LDL) play a critical role in the pathogenesis of atherosclerosis. The activation of circulating leukocytes and their adhesion to the vascular endothelium in response to acute stimuli characterize the first step in initiation of an acute inflammatory response. Through the action of degranulation products, adherent leukocytes induce vascular hyperpermeability and contribute to vascular injury. So, we have investigated the neutrophil adhesion to vascular endothelium, a constant feature of early atherogenesis and transendothelial migration of neutrophil induced by ox-LDL. METHOD: In a series of experiments, human umbilical vascular endothelial cells (HUVECs) were incubated for 24 h after addition of native human LDL (100 ug/mL) and of ox-LDL (100 ug/mL) to the medium. The adherence of 51Cr-labeled neutrophils to endothelial monolayers was measured by neutrophil adhesion assay. For diapedesis experiments, HUVECs were grown to confluence on 8.0um pore cell culture inserts. 51Cr-labeled neutrophils were added to the apical surface of HUVEC monolayers and allowed to migrate into the lower chamber for 3 h under the same preparations of native and oxidized LDLs. Reaults: The secretion of IL-8 depended on the concentration of IL-1a and LPS used to stimulate endothelial monolayers in vitro. In addition, ox-LDL triggered secretion of IL-8 from cultured HUVECs compared to that of n-LDL (867.6 pg/mL vs. 273.1 pg/mL, p<0.01). Increased adherence of neutrophils to HUVECs vs observed with ox-LDL preparation compared to native LDL preparation (36.8+1.5% vs. 25.9+1.7%, p<0.05). Similarly, neutrophil migration across cultured endothelial monolayers was also significantly increased by ox-LDL (48.7+3.8% vs. 34.4+2.9%, p<0.05). CONCLUSION: These results show that ox-LD1. can induce increased neutrophil adhesion and migration through IL-8, a potent effector of neutophil functions, secreted by stimulated endothelial cells. So, we suggest that ox-LDL may affect many components of the atherogenic process, including the early step in the initiation of m acute inflammation of vascular endothelial cells.

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