Cholesterol homeostasis in the hepatocyte.

Authors

Justine Cole, Iana Pencina, Robert Kiss, Rafael Zubiran, Allan D Sniderman

Published in

Journal of clinical lipidology. Sep 15, 2026. Epub Sep 15, 2026.

Abstract

Hepatocytes must maintain both intracellular and whole-body cholesterol homeostasis. The conventional model of cholesterol homeostasis is based on studies in fibroblasts, a cell with limited inputs and outputs of cholesterol. In contrast to fibroblasts and other peripheral cells, cholesterol enters and exits the hepatocyte by multiple pathways. Accordingly, regulation of cholesterol homeostasis should not be assumed to be identical in peripheral cells and hepatocytes. BODY: At steady state, the mass of cholesterol that enters the hepatocyte in chylomicrons and high-density lipoprotein (HDL) approximates the mass of cholesterol excreted from the organism by hepatocytes per day. But this does not include the cholesterol delivered within apolipoprotein B-100 (apoB100) particles. This creates a substantial apparent imbalance between the cholesterol delivered to and excreted from the hepatocyte per day. Furthermore, substantial increases in cholesterol delivered to the hepatocyte in low-density lipoprotein do not result in substantial reductions in the synthesis of cholesterol or expression of low-density lipoprotein receptor, whereas uptake of chylomicron remnants does. The disposition of cholesterol from HDL particles also appears to follow a separate metabolic route within the hepatocyte.
This analysis challenges the validity of the conventional model of cholesterol homeostasis in the hepatocyte. We hypothesize that the cholesterol delivered in apoB100 particles is largely channeled within the hepatocyte to be re-secreted in newly assembled apoB100 particles without this cholesterol fully equilibrating with the regulatory pool of cholesterol. The evidence for the channel model we envisage is incomplete. However, failure of the conventional model should stimulate new efforts to account for cholesterol homeostasis in hepatocytes.

PMID:
42934044
Bibliographic data and abstract were imported from PubMed on 27 Oct 2026.

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