Preprint Review Version 1 This version is not peer-reviewed

A Newly Integrated Model for Intestinal Cholesterol Absorption and Efflux Infers How Plant Sterol Intake Reduces Circulating Cholesterol Levels

Version 1 : Received: 18 September 2018 / Approved: 18 September 2018 / Online: 18 September 2018 (10:46:34 CEST)

How to cite: Nakano, T.; Inoue, I.; Murakoshi, T. A Newly Integrated Model for Intestinal Cholesterol Absorption and Efflux Infers How Plant Sterol Intake Reduces Circulating Cholesterol Levels. Preprints 2018, 2018090345 (doi: 10.20944/preprints201809.0345.v1). Nakano, T.; Inoue, I.; Murakoshi, T. A Newly Integrated Model for Intestinal Cholesterol Absorption and Efflux Infers How Plant Sterol Intake Reduces Circulating Cholesterol Levels. Preprints 2018, 2018090345 (doi: 10.20944/preprints201809.0345.v1).

Abstract

Hypercholesterolemia accelerates atherosclerosis, and extensive research has been undertaken to ameliorate this abnormality. Plant sterols have been shown to inhibit cholesterol absorption and lower plasma cholesterol level since the 1950s. This ingredient has recently been reappraised as a food additive that can be taken daily in a preclinical period to prevent hypercholesterolemia, considering that cardiovascular-related diseases are the top cause of death globally even with clinical interventions. Intestinal cholesterol handling is still elusive, making it difficult to clarify the mechanism for plant sterol-mediated inhibition. Notably, although the small intestine absorbs cholesterol, it is also the organ that excretes it abundantly, via trans-intestinal cholesterol efflux (TICE). In this review, we show a model where the brush border membrane (BBM) of intestinal epithelial cells stands as the dividing ridge for cholesterol fluxes, making cholesterol absorption and TICE inversely correlated. With this model, we tried to explain the plant sterol-mediated inhibitory mechanism. As well as cholesterol, plant sterols diffuse into the BBM but are effluxed back to the lumen rapidly. We propose that repeated plant sterol shuttling between the BBM and lumen promotes cholesterol efflux, and plant sterol in the BBM may disturb the trafficking machineries that transport cholesterol to the cell interior.

Subject Areas

ATP-binding cassette G5/G8; brush border membrane; cholesterol absorption; Niemann-Pick C1-like 1; phytosterols; trans-intestinal cholesterol efflux; fecal neutral sterol excretion

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