Abstract
Obesity is a well-established risk factor for atherosclerosis. However, the mechanistic link between accumulation of adipose tissue and development of atherosclerosis is not clear. Adipose tissue comprises various depots including white adipose tissue (WAT), brown adipose tissue (BAT) and thoracic and abdominal perivascular adipose tissue (PVAT). The phenotype of thoracic PVAT resembles BAT, whereas abdominal PVAT is more like WAT. Here, we review the distinct roles of the adipose tissue depots in the development of atherosclerosis with the ultimate aim to understand how these can be targeted to reduce atherosclerosis. In obesity, increased fatty acid release by WAT and decreased lipid combustion by BAT and thoracic PVAT lead to hyperlipidaemia, which contributes to atherosclerosis development. Besides, obese WAT and abdominal PVAT release pro-inflammatory factors that further promote atherosclerosis. To discourage atherosclerosis development, strategies that reduce the release of pro-inflammatory factors and fatty acids from WAT and abdominal PVAT, or increase combustion of fatty acids by activation of BAT and thoracic PVAT and beiging of WAT are probably most efficient. Possible therapies could include anti-inflammatory compounds such as adiponectin and salicylates to lower inflammation, and β3-adrenergic receptor activators to increase fatty acid combustion. Additional and more specific strategies to promote fatty acid combustion are currently subject of investigation. In conclusion, different adipose depots differentially affect atherosclerosis development, in which atherosclerosis is promoted by energy-storing adipose depots and attenuated by energy-combusting adipose tissue. In obesity, combining therapies that reduce inflammation and increase combustion of lipids are most conceivable to restrain atherogenesis.
Highlights
Cardiovascular disease (CVD) is the leading cause of death worldwide (Finegold et al, 2013), and atherosclerosis is the pathology underlying most cardiovascular events
In contrast to white adipose tissue (WAT), which likely contributes to atherosclerosis as mentioned above, brown adipose tissue (BAT) is increasingly recognized as a potential target to reduce atherosclerosis development
WAT, BAT and perivascular adipose tissue (PVAT) play important albeit tissuespecific roles in the development of atherosclerosis
Summary
Cardiovascular disease (CVD) is the leading cause of death worldwide (Finegold et al, 2013), and atherosclerosis is the pathology underlying most cardiovascular events. Obesity is a major risk factor for CVD (Fox et al, 2008). The underlying biological mechanism between accumulation of adipose tissue and atherosclerosis is not fully understood. Obesity is associated with hyperlipidaemia (Klop et al, 2013; Nordestgaard, 2016) and systemic inflammation (Hotamisligil, 2006; Shoelson et al, 2006), both of which are risk factors for atherosclerosis. Distinct adipose tissue types have specific functions that differentially influence atherosclerosis development. More insight into the relation between adipose tissue types and atherosclerosis will provide novel targets to treat (obese) individuals with high risk of CVD. We aim to review recent advances in research on the role of different adipose tissue types, i.e. white, brown and perivascular adipose tissue, in atherosclerosis, and the ensuing therapeutic implications
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