Aster-dependent nonvesicular transport facilitates dietary cholesterol uptake
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 Y, Cui L, Bedard AH, Sandhu J, Lee SD, Fairall L, Williams KJ, Song W, Munguia P, Russell RA, Martin MG, Jung ME, Jiang H, Schwabe JWR, Young SG, Tontonoz P
Science (New York, N.Y.) · 56 citas
Cómo se estudió
- Diseño
- Estudio en animales (clasificado por nuestro filtro de IA)
- Estudiado en
- Animales
- Resultado principal
- Marcadores de salud y funcionamiento
Quién lo pagó
- Financiación
- Financiación independiente
- Organización sin fines de lucro
- American Diabetes Association
- Organización sin fines de lucro
- American Heart Association
- Organización sin fines de lucro
- Damon Runyon Cancer Research Foundation
- Gobierno
- Australian Government
- Universidad u hospital
- UCSD-UCLA Diabetes Research Center
- Organización sin fines de lucro
- Fondation Leducq
- Universidad u hospital
- Wuhan University
- Gobierno
- National Institutes of Health
- Universidad u hospital
- University of California, San Diego
- Gobierno
- National Heart, Lung, and Blood Institute
- Gobierno
- National Institute of Diabetes and Digestive and Kidney Diseases
- Gobierno
- Eunice Kennedy Shriver National Institute of Child Health and Human Development
- Gobierno
- NICHD NIH HHS
- Gobierno
- NIDDK NIH HHS
- Gobierno
- NHLBI NIH HHS
- Subvenciones
- National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK126779); American Heart Association (903306); National Institute of Diabetes and Digestive and Kidney Diseases (P30-DK063491); National Heart, Lung, and Blood Institute (P01 HL146358); National Institutes of Health (NIH K12); National Heart, Lung, and Blood Institute (R35 HL139725); National Institute of Diabetes and Digestive and Kidney Diseases (T32DK007180); University of California, San Diego (DK063491); Eunice Kennedy Shriver National Institute of Child Health and Human Development (K12 HD111040); National Institute of Diabetes and Digestive and Kidney Diseases (RC2 DK118640); National Institutes of Health (T32DK007180); National Institutes of Health (DK126779); National Institutes of Health (DK-063491); National Institutes of Health (HL146358)
Según 15 financiadores declarados.
Publicación
- Publicado
- 2023-11-09 · Science · vol. 382 · número 6671 · pág. eadf0966
- Editorial
- American Association for the Advancement of Science
- Citado
- 59 citas · más que el 98% de estudios similares · 14.6× el promedio de su campo
- Impacto
- Entre el 10 % más citado de su campo
- Referencias
- 69 trabajos
- Acceso
- Acceso abierto (copia en repositorio)
- Áreas de investigación
- Drug Transport and Resistance Mechanisms · Cholesterol and Lipid Metabolism · Glycosylation and Glycoproteins Research
- Palabras clave
- Cholesterol, Advanced Spaceborne Thermal Emission and Reflection Radiometer, Endoplasmic reticulum, Brush border, Biology, Chemistry, Biochemistry, Internal medicine, Cell biology, Membrane, Medicine
- MeSH
- enterocytes, jejunum, animals, mice, inbred c57bl, mice, knockout, humans, mice, cholesterol, dietary, membrane transport proteins, membrane proteins, biological transport, intestinal absorption, liver x receptors
28 autores
- Alessandra Ferrari🇺🇸 · autor de correspondenciaUniversity of California, Los Angeles
- Emily C. Whang🇺🇸 · autor de correspondenciaUniversity of California, Los Angeles
- Xiao Xu🇺🇸University of California, Los Angeles
- John Paul Kennelly🇺🇸University of California, Los Angeles
- Beatriz Romartínez-Alonso🇬🇧University of Leicester
- Julia J. Mack🇺🇸University of California, Los Angeles
- Thomas A. Weston🇺🇸University of California, Los Angeles
- Kai Chen🇦🇺🇭🇰The University of Western Australia; University of Hong Kong
- Young-Jae Kim🇺🇸University of California, Los Angeles
- Marcus J. Tol🇺🇸University of California, Los Angeles
- Lara Bideyan🇺🇸University of California, Los Angeles
- Alexander H. Nguyen🇺🇸University of California, Los Angeles
- Yajing Gao🇺🇸University of California, Los Angeles
- Liujuan Cui🇺🇸University of California, Los Angeles
- Alexander H. Bedard🇺🇸University of California, Los Angeles
- Jaspreet S. Sandhu🇺🇸University of California, Los Angeles
- Stephen D. Lee🇺🇸University of California, Los Angeles
- Louise Fairall🇬🇧University of Leicester
- Kevin J. Williams🇺🇸University of California, Los Angeles
- Wenxin Song🇺🇸University of California, Los Angeles
- Priscilla Munguia🇺🇸University of California, Los Angeles
- Robert A. Russell🇦🇺Australian Nuclear Science and Technology Organisation; National Deuteration Facility
- Martı́n G. Martı́n🇺🇸University of California, Los Angeles
- Michael E. Jung🇺🇸University of California, Los Angeles
- Haibo Jiang🇦🇺🇭🇰The University of Western Australia; University of Hong Kong
- John W. R. Schwabe🇬🇧University of Leicester
- Stephen G. Young🇺🇸University of California, Los Angeles
- Peter Tontonoz🇺🇸 · autor de correspondenciaUniversity of California, Los Angeles
Resumen
El texto original del estudio, en el idioma en que se publicó.
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.
Resumen vía Europe PMC. Los derechos de autor siguen siendo de los autores o la editorial.
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