Abstract
ObjectivesObesity 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.MethodsOb/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.ResultsOb/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).ConclusionObesity 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.
Highlights
Obesity is a no longer a condition restricted to Western populations but is recognised as a world-wide pandemic
SR-BI-mediated cholesterol efflux was elevated from ob/ob mice and high density lipoproteins (HDL)-c were higher (60%, p
Ex vivo cholesterol efflux was reduced in ob/ob liver and adipose tissue towards apoA-I and HDL
Summary
Obesity is a no longer a condition restricted to Western populations but is recognised as a world-wide pandemic. Adipocytes become dysfunctional, likely due to excessive lipid accumulation and results in excess free fatty acid (FFA) and pro-inflammatory cytokine production. These adipocytokines have downstream effects such as polarisation of resident macrophages to an inflammatory phenotype, changing adipocyte function and recruitment of more macrophages to adipose tissue [5]. This results in a cascade of pro-inflammatory cytokine production/secretion and if left unchecked may initiate and/or contribute to atherogenesis [6]
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