Scientific article
Open access

Steatosis Alters the Activity of Hepatocyte Membrane Transporters in Obese Rats

Published inCells, vol. 10, no. 10, 2733
Publication date2021-10-13
First online date2021-10-13

Fat accumulation (steatosis) in ballooned hepatocytes alters the expression of membrane transporters in Zucker fatty (fa/fa) rats. The aim of the study was to quantify the functions of these transporters and their impact on hepatocyte concentrations using a clinical hepatobiliary contrast agent (Gadobenate dimeglumine, BOPTA) for liver imaging. In isolated and perfused rat livers, we quantified BOPTA accumulation and decay profiles in fa/+ (normal) and fa/fa hepatocytes by placing a gamma counter over livers. Profiles of BOPTA accumulation and decay in hepatocytes were analysed with nonlinear regressions to characterise BOPTA influx and efflux across hepatocyte transporters. At the end of the accumulation period, BOPTA hepatocyte concentrations and influx clearances were not significantly different in fa/+ and fa/fa livers. In contrast, bile clearance was significantly lower in fatty hepatocytes while efflux clearance back to sinusoids compensated the low efflux into canaliculi. The time when BOPTA cellular efflux impacts the accumulation profile of hepatocyte concentrations was slightly delayed (2 min) by steatosis, anticipating a delayed emptying of hepatocytes. The experimental model is useful for quantifying the functions of hepatocyte transporters in liver diseases.

  • Hepatocyte concentrations
  • Hepatocyte membrane transporter
  • Liver imaging
  • Transporter activity
  • Animals
  • Bile Acids and Salts / metabolism
  • Bile Canaliculi / drug effects
  • Bile Canaliculi / metabolism
  • Fatty Liver / metabolism
  • Fatty Liver / pathology
  • Hepatocytes / drug effects
  • Hepatocytes / metabolism
  • Hepatocytes / pathology
  • Liver / drug effects
  • Liver / metabolism
  • Meglumine / analogs & derivatives
  • Meglumine / pharmacokinetics
  • Meglumine / pharmacology
  • Membrane Transport Proteins / metabolism
  • Obesity / metabolism
  • Obesity / pathology
  • Organometallic Compounds / pharmacokinetics
  • Organometallic Compounds / pharmacology
  • Perfusion
  • Rats
  • Rats, Zucker
  • Rheology / drug effects
  • Swiss National Science Foundation - Regulation of the hepatic transporters Oatps and Mrp2: implications for liver imaging and hepatic cholestasis
Citation (ISO format)
PASTOR, Catherine, VILGRAIN, Valérie. Steatosis Alters the Activity of Hepatocyte Membrane Transporters in Obese Rats. In: Cells, 2021, vol. 10, n° 10, p. 2733. doi: 10.3390/cells10102733
Main files (1)
Article (Published version)
ISSN of the journal2073-4409

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