Cholesterol crystallization within hepatocyte lipid droplets and its role in murine NASH
Ioannou GN, Subramanian S, Chait A, Haigh WG, Yeh MM, Farrell GC, Lee SP, Savard C
Journal of lipid research · 152 citas
Etiquetas de revisión
Solo mecanismosDatos neutrales que nuestra revisión registró sobre cómo se hizo este estudio. Describen el método, nunca si nos gusta el resultado.
Cómo se estudió
- Diseño
- Estudio en animales (clasificado por nuestro filtro de IA)
- Estudiado en
- Personas, más trabajo en animales o laboratorio
- Resultado principal
- Solo mecanismos
Quién lo pagó
- Financiación
- Financiación independiente
- Gobierno
- U.S. Department of Veterans Affairs
- Universidad u hospital
- University of Washington
- Universidad u hospital
- Diabetes Research Center, University of Washington
- Gobierno
- National Institute of Diabetes and Digestive and Kidney Diseases
- Gobierno
- NIDDK NIH HHS
- Gobierno
- BLRD VA
- Gobierno
- Veterans Affairs Biomedical and Laboratory Research and Development
- Subvenciones
- National Institute of Diabetes and Digestive and Kidney Diseases (P30‐DK‐017047); U.S. Department of Veterans Affairs (I01 BX002910)
Según 7 financiadores declarados.
Publicación
- Publicado
- 2017-04-13 · J Lipid Res · vol. 58 · número 6 · págs. 1067–1079
- Editorial
- Elsevier BV
- Citado
- 180 citas · más que el 97% de estudios similares · 5.5× el promedio de su campo
- Impacto
- Entre el 10 % más citado de su campo
- Referencias
- 50 trabajos
- Acceso
- Acceso abierto (revista híbrida) · CC-BY
- Áreas de investigación
- Lipid metabolism and biosynthesis · Liver Disease Diagnosis and Treatment · Sphingolipid Metabolism and Signaling
- Palabras clave
- Cholesterol, Lipid droplet, Chemistry, Hepatocyte, Reverse cholesterol transport, Internal medicine, Endocrinology, Steatosis, Biochemistry, Lipoprotein, Biology, Medicine, In vitro
- MeSH
- kupffer cells, hepatocytes, animals, mice, inbred c57bl, humans, mice, cholesterol, cholesterol, dietary, crystallization, enzyme activation, dose-response relationship, drug, male, hep g2 cells, diet, high-fat, non-alcoholic fatty liver disease, lipid droplets, thp-1 cells
8 autores
- George N. Ioannou🇺🇸 · autor de correspondenciaUniversity of Washington; VA Puget Sound Health Care System
- Savitha Subramanian🇺🇸University of Washington
- Alan Chait🇺🇸University of Washington
- W. Geoffrey Haigh🇺🇸VA Puget Sound Health Care System
- Matthew M. Yeh🇺🇸University of Washington
- Geoffrey C. Farrell🇦🇺Australian National University; Canberra Hospital
- Sum P. Lee🇺🇸University of Washington
- Christopher E. Savard🇺🇸University of Washington; VA Puget Sound Health Care System
Resumen
El texto original del estudio, en el idioma en que se publicó.
We recently reported that cholesterol crystals form in hepatocyte lipid droplets (LDs) in human and experimental nonalcoholic steatohepatitis. Herein, we assigned WT C57BL/6J mice to a high-fat (15%) diet for 6 months, supplemented with 0%, 0.25%, 0.5%, 0.75%, or 1% dietary cholesterol. Increasing dietary cholesterol led to cholesterol loading of the liver, but not of adipose tissue, resulting in fibrosing steatohepatitis at a dietary cholesterol concentration of ≥0.5%, whereas mice on lower-cholesterol diets developed only simple steatosis. Hepatic cholesterol crystals and crown-like structures also developed at a dietary cholesterol concentration ≥0.5%. Crown-like structures consisted of activated Kupffer cells (KCs) staining positive for NLRP3 and activated caspase 1, which surrounded and processed cholesterol crystal-containing remnant LDs of dead hepatocytes. The KCs processed LDs at the center of crown-like structures in the extracellular space by lysosomal enzymes, ultimately transforming into lipid-laden foam cells. When HepG2 cells were exposed to LDL cholesterol, they developed cholesterol crystals in LD membranes, which caused activation of THP1 cells (macrophages) grown in coculture; upregulation of TNF-alpha, NLRP3, and interleukin 1beta (IL1β) mRNA; and secretion of IL-1beta. In conclusion, cholesterol crystals form on the LD membrane of hepatocytes and cause activation and cholesterol loading of KCs that surround and process these LDs by lysosomal enzymes.
Resumen vía Europe PMC. Los derechos de autor siguen siendo de los autores o la editorial (CC BY).
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