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.
Abbreviations:
ABC (ATP-binding cassette transporters), apo (apolipoprotein), CVD (cardiovascular disease), HDL (high-density lipoprotein), HDL-C (HDL cholesterol), LDL (low-density lipoprotein), LDL-C (LDL cholesterol), m-RCT (in vivo macrophage-specific reverse cholesterol transport), T2D (type 2 diabetes mellitus)To read this article in full you will need to make a payment
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Article info
Publication history
Published online: May 17, 2017
Accepted:
May 11,
2017
Received:
March 3,
2017
Identification
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© 2017 Elsevier Inc. All rights reserved.
