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  • Pioglitazone reduces lipid droplets in cholesterolosis of the gallbladder by increasing ABCA1 and NCEH1 expression.

Pioglitazone reduces lipid droplets in cholesterolosis of the gallbladder by increasing ABCA1 and NCEH1 expression.

Molecular and cellular biochemistry (2014-10-05)
Jing-Min Wang, Dong Wang, Yu-Yan Tan, Gang Zhao, Zhen-Ling Ji
ABSTRACT

As a cholesterol-induced metabolic disease, cholesterolosis of the gallbladder is often resected clinically, which could lead to many complications. The histopathology of cholesterolosis is due to excessive lipid droplet accumulation in epithelial and subcutaneous tissues. The main components of lipid droplets are cholesterol esters (CEs). Removal of CEs from gallbladder epithelial cells (GBECs) is very important for maintaining intracellular cholesterol homeostasis and for treating cholesterol-related diseases. In this study, pioglitazone was used to reduce intracellular CEs. To further elucidate the mechanism, cholesterolosis GBECs were treated with pioglitazone, 22-(R)-hydroxycholesterol (a liver X receptor α (LXRα) agonist), or peroxisome proliferator-activated receptor gamma (PPARγ) siRNA. Western blotting for PPARγ, LXRα, ATP-binding cassette transporter A1 (ABCA1), and neutral cholesteryl ester hydrolase 1 (NCEH1) was performed. At length, cholesterol efflux to apoA-I was measured, and oil red O staining was used to visualize lipid droplet variations in cells. In conclusion, we observed that pioglitazone increased ABCA1 expression in an LXR-dependent manner and NCEH1 expression in an LXRα-independent manner, which mobilized CE hydrolysis and cholesterol efflux to reduce lipid droplet content in cholesterolosis GBECs. Our data provide a plausible alternative to human gallbladder cholesterolosis.

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22(R)-Hydroxycholesterol, ≥98%
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Pioglitazone for system suitability, European Pharmacopoeia (EP) Reference Standard
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Thiazolyl Blue Tetrazolium Bromide, 98%
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Thiazolyl Blue Tetrazolium Bromide, powder, BioReagent, suitable for cell culture, suitable for insect cell culture, ≥97.5% (HPLC)
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250 g
Estimated to ship on March 24, 2025
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Sigma-Aldrich
Pioglitazone hydrochloride, ≥98% (HPLC)
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250 g
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$333.00
2.5 kg
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$1,670.00
USP
Pioglitazone hydrochloride, United States Pharmacopeia (USP) Reference Standard
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250 g
Estimated to ship on March 24, 2025
$333.00
2.5 kg
Estimated to ship on March 24, 2025
$1,670.00
Pioglitazone hydrochloride, European Pharmacopoeia (EP) Reference Standard
Sign Into View Organizational & Contract Pricing
SKUPack SizeAvailabilityPriceQuantity
250 g
Estimated to ship on March 24, 2025
$333.00
2.5 kg
Estimated to ship on March 24, 2025
$1,670.00