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Publication
Obesity potentiates development of fatty liver and insulin resistance, but not
atherosclerosis, in high-fat diet-fed agouti LDLR-deficient mice.
Authors Coenen KR, Hasty AH
Submitted By Alyssa Hasty on 11/6/2007
Status Published
Journal American journal of physiology. Endocrinology and metabolism
Year 2007
Date Published
Volume : Pages 293 : E492 - E499
PubMed Reference 17566116
Abstract Obesity is increasing at an alarming rate, and its related disorders are placing
a considerable strain on our healthcare system. Although they are not always
coincident, obesity is often accompanied by hyperlipidemia. Both obesity and
hyperlipidemia are independently associated with atherosclerosis, nonalcoholic
fatty liver disease (NAFLD), and insulin resistance (IR). Thus, we sought to
determine the relative contributions of obesity and hyperlipidemia to these
associated pathologies. Obese agouti (A(y)/a) mice and their littermate controls
(a/a) were placed on an LDL receptor (LDLR)(-/-) background. At 4 mo of age,
mice were either maintained on chow diet (CD) or placed on Western diet (WD) for
12 wk. These genetic and dietary manipulations yielded four experimental groups:
1) lean, a/a;LDLR(-/-)CD; 2) genetic-induced obesity (GIO), A(y)/a;LDLR(-/-)CD;
3) diet-induced obesity (DIO), a/a;LDLR(-/-)WD; and 4) genetic- plus
diet-induced obesity (GIO/DIO), A(y)/a;LDLR(-/-)WD. Lipoprotein profiles
revealed increased VLDL and LDL particles in WD-fed mice compared with CD-fed
controls. The hyperlipidemia present in this mouse model was the result of both
increased hepatic triglyceride production and delayed lipoprotein clearance from
the plasma. Both WD-fed groups exhibited similar levels of atherosclerotic
lesion area, with increased obesity in the GIO/DIO group having no impact on
atherogenesis. However, the severe obesity in the GIO/DIO group did aggravate
NAFLD and IR. These findings suggest that, although obesity and hyperlipidemia
exert individual pathological effects, the combination of the two has the
potential to exert an additive effect on NAFLD and IR but not atherosclerosis in
this mouse model.




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