Abstract
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.
Highlights
We showed previously that hepatocytes in fa/fa livers are distended by large fat droplets [10]
We found that the maximal BOPTA hepatocyte concentrations were similar in fa/+ and fa/fa livers
We showed that a BOPTA-induced return backistoassociated sinusoidswith using hepatocyte accumulation is modulated by bile flow increase is not significantly different in fa/fa and fa/+
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Nonalcoholic fatty liver disease (NAFLD) includes various dysfunctions such as increased intrahepatic triglyceride content (steatosis), inflammation, and fibrosis [1,2]. The transition from fatty livers to more severe disease (steatohepatitis) is triggered by inflammation. Cholestasis (or decreased bile flow) is a marker of severity. Significant progress has been made to decrease the burden of NAFLD, but the translation of experimental treatments to the human disease has consistently failed [3]. One of the reasons is that the mechanisms underlying the disease are numerous and complex. These experimental models contribute to a better understanding of the disease
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