Browsing by Author "Ferrari, A"

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    Aster-dependent nonvesicular transport facilitates dietary cholesterol uptake
    (American Association for the Advancement of Science (AAAS), 2023-11-10) Ferrari, A; Whang, E; Xiao, X; Kennelly, JP; Romartinez-Alonso, B; Mack, JJ; Weston, T; Chen, K; Kim, Y; Tol, MJ; Bideyan, L; Nguyen, A; Gao, YJ; Cui, LJ; Bedard, AH; Sandhu, J; Lee, SD; Fairall, L; Williams, KJ; Song, WX; Munguia, P; Russell, RA; Martin, MG; Jung, ME; Jiang, H; Schwabe, JWR; Young, SG; Tontonoz, P
    Intestinal absorption is an important contributor to systemic cholesterol homeostasis. Niemann-Pick C1 Like 1 (NPC1L1) assists in the initial step of dietary cholesterol uptake, but how cholesterol moves downstream of NPC1L1 is unknown. We show that Aster-B and Aster-C are critical for nonvesicular cholesterol movement in enterocytes. Loss of NPC1L1 diminishes accessible plasma membrane (PM) cholesterol and abolishes Aster recruitment to the intestinal brush border. Enterocytes lacking Asters accumulate PM cholesterol and show endoplasmic reticulum cholesterol depletion. Aster-deficient mice have impaired cholesterol absorption and are protected against diet-induced hypercholesterolemia. Finally, the Aster pathway can be targeted with a small-molecule inhibitor to manipulate cholesterol uptake. These findings identify the Aster pathway as a physiologically important and pharmacologically tractable node in dietary lipid absorption. © 2023 The Authors, exclusive licensee American Association for the Advancement of Science.
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    NanoSIMS imaging of lipid absorption by intestinal enterocytes
    (Elsevier, 2022-11-14) Chen, K; Song, WX; Russell, RA; Ferrari, A; Darwish, TA; Tontonoz, P; Young, SG; Jiang, H
    Absorption of lipids by intestinal enterocytes is crucial for growth and development and is highly relevant to human metabolic diseases. Hence, the molecules and mechanisms for lipid absorption have been studied intensively. Electron microscopy has been useful for exploring intestinal lipid absorption (1), but high-resolution images of the absorption of specific lipids have been lacking. © 2022 The Authors. Published by Elsevier Inc on behalf of the American Society for Biochemistry and Molecular Biology. This is an open access article under the CC BY licence.