Induction of obesity impairs reverse cholesterol transport in ob/ob mice

My Ngan Duong, Kiyoko Uno, Victoria Nankivell, Christina Bursill, Stephen J. Nicholls

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Abstract

Objectives Obesity is an independent risk factor for cardiovascular disease. Reverse cholesterol transport (RCT) is an important cardioprotective mechanism. This study aimed to investigate RCT changes in a murine model of obesity. Methods Ob/ob and control mice were injected with [3H]-cholesterol-labelled macrophages and cholesterol accumulation quantified after 48 h. Ex vivo, cholesterol efflux and uptake were determined in hepatic and adipose tissues. Results Ob/ob mice had more labelled cholesterol in their plasma (86%, p<0.001), suggesting impaired RCT. SR-BI-mediated cholesterol efflux was elevated from ob/ob mice (serum, 33%; apoB-depleted plasma, 14%, p<0.01) and HDL-c were also higher (60%, p<0.01). Ex vivo it was found that cholesterol uptake was significantly lower into the livers and adipose tissue of ob/ob mice, compared to non-obese wildtype controls. Furthermore, ex vivo cholesterol efflux was reduced in ob/ob liver and adipose tissue towards apoA-I and HDL. Consistent with this, protein levels of SR-BI and ABCG1 were significantly lower in ob/ob hepatic and adipose tissue than in wildtype mice. Finally, labelled cholesterol concentrations were lower in ob/ob bile (67%, p<0.01) and faeces (76%, p<0.0001). Conclusion Obesity causes impairment in RCT due to reduced plasma cholesterol uptake and efflux by hepatocytes and adipocytes. A reduction in the capacity for plasma cholesterol clearance may partly account for increased CVD risk with obesity.

Original languageEnglish
Article numbere0202102
Number of pages17
JournalPLoS ONE
Volume13
Issue number9
DOIs
Publication statusPublished - 1 Sep 2018
Externally publishedYes

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