کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5684926 | 1597924 | 2017 | 58 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
LXR-dependent regulation of macrophage-specific reverse cholesterol transport is impaired in a model of genetic diabesity
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کلمات کلیدی
ABCHDLLDL-CHDL-CT2DATP-binding cassette transporters - ATP گیرنده های کاسه اتصالhigh-density lipoprotein - HDL یا لیپوپروتئین با دانسیته بالا یا چگالی بالاapo - آپوapolipoprotein - آپولیپوپروتئینcardiovascular disease - بیماری قلب و عروقیType 2 diabetes mellitus - دیابت نوع دوCVD - رسوب دهی شیمیایی بخار Low-density lipoprotein - لیپوپروتئین کم چگالی یا الدیال LDL - لیپوپروتئین کم چگالی(کلسترول بد)HDL cholesterol - کلسترول HDLLDL cholesterol - کلسترول LDL
موضوعات مرتبط
علوم پزشکی و سلامت
پزشکی و دندانپزشکی
پزشکی و دندانپزشکی (عمومی)
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Diabesity and fatty liver have been associated with low levels of high-density lipoprotein cholesterol, and thus could impair macrophage-specific reverse cholesterol transport (m-RCT). Liver X receptor (LXR) plays a critical role in m-RCT. Abcg5/g8 sterol transporters, which are involved in cholesterol trafficking into bile, as well as other LXR targets, could be compromised in the livers of obese individuals. We aimed to determine m-RCT dynamics in a mouse model of diabesity, the db/db mice. These obese mice displayed a significant retention of macrophage-derived cholesterol in the liver and reduced fecal cholesterol elimination compared with nonobese mice. This was associated with a significant downregulation of the hepatic LXR targets, including Abcg5/g8. Pharmacologic induction of LXR promoted the delivery of total tracer output into feces in db/db mice, partly due to increased liver and small intestine Abcg5/Abcg8 gene expression. Notably, a favorable upregulation of the hepatic levels of ABCG5/G8 and NR1H3 was also observed postoperatively in morbidly obese patients, suggesting a similar LXR impairment in these patients. In conclusion, our data show that downregulation of the LXR axis impairs cholesterol transfer from macrophages to feces in db/db mice, whereas the induction of the LXR axis partly restores impaired m-RCT by elevating the liver and small intestine expressions of Abcg5/g8.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Translational Research - Volume 186, August 2017, Pages 19-35.e5
Journal: Translational Research - Volume 186, August 2017, Pages 19-35.e5
نویسندگان
Teresa L. Errico, Karen Alejandra Méndez-Lara, David Santos, Núria Cabrerizo, LucÃa Baila-Rueda, Jari Metso, Ana Cenarro, Eva Pardina, Albert Lecube, Matti Jauhiainen, Julia Peinado-Onsurbe, Joan Carles Escolà -Gil, Francisco Blanco-Vaca, Josep Julve,