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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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
Issue number9
Publication statusPublished - 1 Sept 2018
Externally publishedYes

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