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The role of adipose tissue in cardiovascular health and disease

Abstract

Accumulating knowledge on the biology and function of the adipose tissue has led to a major shift in our understanding of its role in health and disease. The adipose tissue is now recognized as a crucial regulator of cardiovascular health, mediated by the secretion of several bioactive products, including adipocytokines, microvesicles and gaseous messengers, with a wide range of endocrine and paracrine effects on the cardiovascular system. The adipose tissue function and secretome are tightly controlled by complex homeostatic mechanisms and local cell–cell interactions, which can become dysregulated in obesity. Systemic or local inflammation and insulin resistance lead to a shift in the adipose tissue secretome from anti-inflammatory and anti-atherogenic towards a pro-inflammatory and pro-atherogenic profile. Moreover, the interplay between the adipose tissue and the cardiovascular system is bidirectional, with vascular-derived and heart-derived signals directly affecting adipose tissue biology. In this Review, we summarize the current knowledge of the biology and regional variability of adipose tissue in humans, deciphering the complex molecular mechanisms controlling the crosstalk between the adipose tissue and the cardiovascular system, and their possible clinical translation. In addition, we highlight the latest developments in adipose tissue imaging for cardiovascular risk stratification and discuss how therapeutic targeting of the adipose tissue can improve prevention and treatment of cardiovascular disease.

Key points

  • The adipose tissue is a crucial regulator of cardiovascular health and exerts both protective and deleterious effects on the cardiovascular system.

  • The biological profile of the adipose tissue largely depends on its expansion, body distribution and quality and differences in local biology.

  • The adipose tissue can affect local cardiovascular biology through the secretion of adipocytokines with endocrine and/or paracrine effects.

  • Conversely, pro-inflammatory and oxidative stimuli in diseased vessels and/or myocardium can modify adipose tissue biology, suggesting a bidirectional interplay between the adipose tissue and the cardiovascular system.

  • Several traditional and experimental imaging modalities can be exploited to characterize both quantitative and qualitative adipose tissue features with important implications in cardiometabolic risk stratification.

  • The adipose tissue is a promising therapeutic target in cardiovascular therapeutics and might mediate the cardiovascular benefit observed with different pharmacological, lifestyle and other types of interventions.

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Fig. 1: Effects of the adipose tissue in the cardiovascular system.
Fig. 2: Interplay between the adipose tissue and the vascular wall.
Fig. 3: Interplay between the adipose tissue and the myocardium.
Fig. 4: Noninvasive imaging for adipose tissue phenotyping.

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Acknowledgements

E.K.O. receives support from the A.G. Leventis Foundation. C.A. received funding from the British Heart Foundation (FS/16/15/32047 and TG/16/3/32687), the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre and the Novo Nordisk Foundation (NNF15CC0018486).

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Nature Reviews Cardiology thanks J. Eckel, G. Iacobellis, H. Morawietz and the other anonymous reviewer(s) for their contribution to the peer review of this work.

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E.K.O. performed the literature review, prepared the figures and tables and wrote the manuscript before submission. C.A. provided scientific direction and wrote and reviewed the manuscript before submission.

Corresponding author

Correspondence to Charalambos Antoniades.

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Competing interests

The methods for analysis of perivascular Fat Attenuation Index described in this manuscript are subject to patent applications (PCT/GB2015/052359 and PCT/GB2017/053262). C.A. is a founder and shareholder of Caristo Diagnostics, a CT-image analysis company. C.A. has received research funding from Novo Nordisk and Sanofi and a consultancy fee from Mitsubishi Tanabe.

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Glossary

Visceral adipose tissue

(VAT). Adipose tissue surrounding the visceral organs in the thorax and abdomen, including fat in the omental and mesenteric peritoneal folds (omental/mesenteric adipose tissue), around the kidneys in the retroperitoneal space (perirenal adipose tissue) and epicardial, pericardial and other depots.

Epicardial adipose tissue

(EAT). The adipose tissue layer that lies between the surface of the heart and the visceral pericardium.

Pericardial adipose tissue

The adipose tissue layer located on the external surface of the parietal pericardium.

White adipose tissue

(WAT). The predominant adipose tissue type found in the human body, which is responsible for energy storage in the form of triglycerides and energy supply to peripheral tissues through regulated release of free fatty acids.

Brown adipose tissue

(BAT). A distinct, metabolically active adipose tissue phenotype that is found predominantly in the interscapular and supraclavicular regions in humans and is involved in thermoregulatory thermogenesis.

Beige adipose tissue

Also known as brite adipose tissue; an inducible, brown-like adipose tissue phenotype, which is normally found interspersed in white adipose tissue depots.

Adipocytokines

A range of bioactive molecules secreted by various cell types found in the adipose tissue (such as adipocytes and stromal cells) that exert autocrine, paracrine and endocrine effects on both the adipose and the peripheral tissues.

Ectopic fat

Fat stored in tissues other than the adipose tissue that normally contain small amounts of fat, such as the heart, liver and muscles.

Perivascular adipose tissue

(PVAT). Adipose tissue surrounding the vessels that is often contiguous to the outer adventitial layer.

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Oikonomou, E.K., Antoniades, C. The role of adipose tissue in cardiovascular health and disease. Nat Rev Cardiol 16, 83–99 (2019). https://doi.org/10.1038/s41569-018-0097-6

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