High-Glucose and Free Fatty Acid-Induced Adipocytes Generate Increasing of HMGB1 and Reduced GLUT4 Expression

Rita Rosita; Yuyun Yueniwati; Agustina Tri Endharti; Mochamad Aris Widodo

doi:10.3889/oamjms.2021.7199

Authors

Rita Rosita Brawijaya University
Yuyun Yueniwati Department of Radiology, Universitas Brawijaya, Malang, Jawa Timur, Indonesia https://orcid.org/0000-0001-9932-2015
Agustina Tri Endharti Department of Parasitology, Faculty of Medicine, Brawijaya University, Malang, Jawa Timur, Indonesia https://orcid.org/0000-0002-2062-5740
Mochamad Aris Widodo Department of Clinical Pharmacology, Faculty of Medicine, Brawijaya University, Malang, Jawa Timur, Indonesia

DOI:

https://doi.org/10.3889/oamjms.2021.7199

Keywords:

Adipocytes, High Glucose, FFA, Necrotic Cell Death, Hypertrophy, Insulin Resistance

Abstract

Background

High-mobility group box 1 protein (HMGB1) is released from necrotic adipocytes into the extracellular milieu as an inflammatory alarmin in obesity. Although the impact of excess nutrient on adipocytes is well known, it is not clear how specific its component drive cell-size and damaged of adipocytes, and how this relates to the risk of insulin resistance.

Objectives

The aim of this study was to determine HMGB1 level in adipocytes cultures after high glucose and/or FFA exposures and to assess GLUT4 expression. We determined cellular features of adipocytes that correlates to HMGB1 released and insulin resistance.

Methods

Differentiated adipocytes were exposed to high glucose and/or FFAs for 7 days. ELISA was performed on supernatant to assess the HMGB1 level. Total GLUT4 expression were quantified by immunofluorescense.

Results

High glucose and FFA-exposed cells have significant increase of HMGB1 level with decreased of cell size and necrotic adipocytes features. The total GLUT4 were reduced in HG-cells (p <0,045), but not in FFA cells. Hypertrophic adipocytes (p <0.05) and slight decrease of GLUT4 expression were showed on HG+FFA exposures with no increase of HMGB1 level. There was a significant correlation between cell size and HMGB1 level (R -0,637, p < 0.026)

Conclusion

The expression level studies between high glucose, FFA, and a combination of both on adipocytes results strongly suggest that high glucose is more damaging to adipocyte compared to FFA. Nevertheless, the combination of the two causes adipocyte dysfunction with general features of adipose tissue in obesity, suggested it can be used as a hypertrophic adipocytes model to study obesity in vitro.

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