ATP7B knockout disturbs copper and lipid metabolism in Caco-2 cells

PloS One
Sarah GuttmannHartmut H Schmidt

Abstract

Intestinal cells control delivery of lipids to the body by adsorption, storage and secretion. Copper (Cu) is an important trace element and has been shown to modulate lipid metabolism. Mutation of the liver Cu exporter ATP7B is the cause of Wilson disease and is associated with Cu accumulation in different tissues. To determine the relationship of Cu and lipid homeostasis in intestinal cells, a CRISPR/Cas9 knockout of ATP7B (KO) was introduced in Caco-2 cells. KO cells showed increased sensitivity to Cu, elevated intracellular Cu storage, and induction of genes regulating oxidative stress. Chylomicron structural protein ApoB48 was significantly downregulated in KO cells by Cu. Apolipoproteins ApoA1, ApoC3 and ApoE were constitutively induced by loss of ATP7B. Formation of small sized lipid droplets (LDs) was enhanced by Cu, whereas large sized LDs were reduced. Cu reduced triglyceride (TG) storage and secretion. Exposure of KO cells to oleic acid (OA) resulted in enhanced TG storage. The findings suggest that Cu represses intestinal TG lipogenesis, while loss of ATP7B results in OA-induced TG storage.

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Citations

Oct 1, 2020·PloS One·Michael PöhlerVanessa Sandfort
Aug 9, 2021·Biochimica Et Biophysica Acta. General Subjects·Bryce BladesSharon La Fontaine

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Methods Mentioned

BETA
PCR
atomic absorption spectroscopy
protein assay
electron microscopy
X-ray

Software Mentioned

GraphPad Prism
SPSS
ImageJ

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