The endocrine function of adipose tissues in health and cardiometabolic disease

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Abstract

In addition to their role in glucose and lipid metabolism, adipocytes respond differentially to physiological cues or metabolic stress by releasing endocrine factors that regulate diverse processes, such as energy expenditure, appetite control, glucose homeostasis, insulin sensitivity, inflammation and tissue repair. Both energy-storing white adipocytes and thermogenic brown and beige adipocytes secrete hormones, which can be peptides (adipokines), lipids (lipokines) and exosomal microRNAs. Some of these factors have defined targets; for example, adiponectin and leptin signal through their respective receptors that are expressed in multiple organs. For other adipocyte hormones, receptors are more promiscuous or remain to be identified. Furthermore, many of these hormones are also produced by other organs and tissues, which makes defining the endocrine contribution of adipose tissues a challenge. In this Review, we discuss the functional role of adipose tissue-derived endocrine hormones for metabolic adaptations to the environment and we highlight how these factors contribute to the development of cardiometabolic diseases. We also cover how this knowledge can be translated into human therapies. In addition, we discuss recent findings that emphasize the endocrine role of white versus thermogenic adipocytes in conditions of health and disease.

Key points

  • White and brown adipocytes secrete many peptide hormones (adipokines), bioactive lipids (lipokines) and RNA molecules with local (paracrine) and systemic (endocrine) effects on the brain, pancreatic β-cells, the liver, skeletal muscle and the cardiovascular system.

  • Production and secretion of adipokines and lipokines is dependent on the energy status of adipose tissues. Through endocrine action, these factors contribute to systemic energy metabolism by regulating appetite, thermogenesis, glucose metabolism and lipid metabolism.

  • Many peptides that were initially described as adipokines are secreted by endothelial and immune cells located in adipose tissues, as well as by other organs, which means the endocrine contribution of adipocytes can be difficult to ascertain.

  • In healthy states, white and brown adipose tissues secrete endocrine factors that maintain organ functions and metabolic homeostasis.

  • In obesity, hypertrophic adipocytes and adipose tissue-resident immune cells accelerate a chronic, proinflammatory profile with altered secretion of adipokines and lipokines, thereby exacerbating cardiometabolic disease.

  • Preclinical and clinical studies show that activating or inhibiting the signalling of specific adipokines or lipokines could be an approach suitable to treat or prevent the development of cardiometabolic diseases. However, in almost all cases, efficacy and safety in humans needs to be proven.

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Fig. 1: Endocrine effects of adipocyte-secreted factors.
Fig. 2: Endocrine factors released by healthy and unhealthy adipose tissues.
Fig. 3: Functional relevance of adipokines and lipokines in cardiometabolic diseases.

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Acknowledgements

The authors acknowledge the support of grants from the Deutsche Forschungsgemeinschaft (SCHE522/4-1), Collaborative Research Center (SFB 1328) and Heisenberg Professorship (HE3645/10-1).

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The authors contributed equally to all aspects of the article.

Correspondence to Joerg Heeren.

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Glossary

Uncoupling protein 1

(UCP1). A unique proton transporter that shuttles protons back into the mitochondrial matrix and uncouples the electron transfer chain from ATP synthesis, a process that generates heat.

M2 macrophages

Macrophages polarized by type 2 immunity-related cytokines such as IL-4 and IL-13, which maintain tissue homeostasis by counteracting proinflammatory processes and facilitating tissue regeneration.

Lipodystrophy

A genetic or acquired condition that is characterized by lack of adipose tissue, insulin resistance and hyperglycaemia.

Neointima

Pathological thickening of the subendothelial layer (intima) of arteries due to atherosclerosis or other arterial injuries

Exosomes

Small cytosol-containing membrane vesicles that are released by one cell to be taken up by other cells and release their content, for example microRNA.

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