In Collections
This item can be found in the following collections:
Sr-Bi deficiency uncouples the development of hypertriglyceridemia and atherosclerosis from hepatic steatosis aand glucose intolerance in obese mice
Scavenger receptor BI (SR-BI) plays a quantitative role in triglyceride
metabolism. However, the relevance of SR-BI in pa- thologies associated with disturbances
in triglyceride homeostasis, i.e. obesity and fatty liver disease, remains largely
unknown. We therefore investigated the metabolic phenotype of SR-BI knockout mice and wild- type
controls after a high-fat diet challenge.
Mice were fed a high-fat diet for 12 weeks.
SR-BI knockout mice gained significantly more weight than wild- type control mice after
12 weeks of high-fat diet feeding (13±1 grams versus 9±1 grams, respectively; P<0.05). SR-BI
deficiency was associated with higher plasma levels of free cholesterol (+111%; P<0.001) and cho-
lesteryl esters (+89%; P<0.001) as well as hypertriglyceridemia (+40%; P<0.01). In
contrast, liver triglyceride levels were lower (-29%; P<0.05) in SR-BI knockout mice, despite
relatively high hepatic...
Scavenger receptor BI (SR-BI) plays a quantitative role in triglyceride
metabolism. However, the relevance of SR-BI in pa- thologies associated with disturbances
in triglyceride homeostasis, i.e. obesity and fatty liver disease, remains largely
unknown. We therefore investigated the metabolic phenotype of SR-BI knockout mice and wild- type
controls after a high-fat diet challenge.
Mice were fed a high-fat diet for 12 weeks.
SR-BI knockout mice gained significantly more weight than wild- type control mice after
12 weeks of high-fat diet feeding (13±1 grams versus 9±1 grams, respectively; P<0.05). SR-BI
deficiency was associated with higher plasma levels of free cholesterol (+111%; P<0.001) and cho-
lesteryl esters (+89%; P<0.001) as well as hypertriglyceridemia (+40%; P<0.01). In
contrast, liver triglyceride levels were lower (-29%; P<0.05) in SR-BI knockout mice, despite
relatively high hepatic expression levels of lipogenic genes ACC (+54%; P<0.05) and SCD1
(+199%; P<0.01). Fasting blood glucose levels were higher in SR-BI knockout mice as compared to
wild-type controls (+20%; P<0.01). However, SR-BI knockout mice could handle an oral bolus of
glucose much better than wild-type mice as judged from the 45% lower (P<0.05) area under the
curve of the oral glucose tolerance test. Notably, atherosclerotic lesions could be
detected in the aortic root of all SR-BI knockout mice, while none were present in wild- type
mice after the high-fat diet challenge.
SR-BI deficiency disassociates hypertriglyceridemia, obesity, and atherosclerosis
development from hepatic steatosis and glucose intolerance in high-fat diet-fed mice. Our
studies provide additional proof
for the biological relevance of SR-BI in total body triglyceride metabolism.
- All authors
- Hoekstra, M.; Ouweneel, A.B.; Nahon, J.E.; Geerling, J.J.; Eck, M. van
- Date
- 2019-08-31
- Volume
- 287
- Pages
- E121 - E121