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January 23, 2024

Pediatric Research Update | Adipokines: Deciphering the cardiovascular signature of adipose tissue.

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Each month, the OMA Pediatric Committee reviews a pediatric-focused obesity research update to help keep you up to date about the latest findings. This month’s update addresses Adipokines.

Adipokines: Deciphering the cardiovascular signature of adipose tissue.

Article Summary

This article is a deep dive into the complex relationship between adipose tissue, hypertension, and heart disease. Adipose tissue is a dynamic complicated organ. The adipokines produced by adipose tissue and the impacts of these signaling molecules on blood pressure regulation and cardiovascular homeostasis are presented.

Article Review

The authors begin by relating hypertension (HTN) to cardiovascular disease (CVD) and then HTN to obesity and lipodystrophy. They then describe the adipose tissue types - white adipose tissue (WAT), brown adipose tissue (BAT), and beige adipose tissue. They stress the location of each adipose tissue type and the cell population. Each type of adipose tissue is a unique endocrine organ and can secrete diverse molecules. All different types of pharmacological receptors are expressed in adipocytes: Ligand-gated ion channels, tyrosine kinase-coupled, intracellular steroid, R-protein-coupled, and trafficking receptors. These receptors control the profile of the adipocytes. The more than 600 bioactive molecules produced by adipose tissue are referred to as adipokines. The authors focus on the most studied; leptin, adiponectin, chimerin, omentin, FGF21, resistin, visfatin, biogenic amines, and antior pro-inflammatory cytokines. Leptin and adiponectin are molecules well-known to obesity medicine practitioners, but the authors stress the links to HTN and CVD. Chimerin, omentin, resistin and visfatin are more recently identified molecules related to adipose tissue, HTN and CVD.

FGF21 is a well-known molecule but the authors bring up some new information related to adipocytes. The biogenic amines are related to the potential functions of perivascular adipose tissue (PVAT) and the relationship between PVAT and vascular endothelium in HTN and CVD. Anti-or proinflammatory cytokines are not only produced by circulating white blood cells but also by adipocytes and tissue specific macrophages. The authors discuss the research needed to work out the details of how adipose tissue impacts circulating cytokines, HTN, and CVD. The authors then address the renin-angiotensinogen-aldosterone system (RAAS) and the ways in which adipose tissue interacts with the RAAS.

Adipose tissue is the second largest producer of angiotensinogen (AGT). Angiotensin II receptors (ATRs) are involved in functional adipocyte differentiation, increased fat mass, higher insulin resistance, and the promotion of inflammatory signaling. Adipocytes can produce aldosterone that can induce impaired endothelial dependent relaxation of blood vessels. Leptin can activate leptin receptors in the adrenal gland and cause production of aldosterone. The authors then discuss how leptin and adiponectin can affect blood pressure control in the CNS and the sympathetic nervous system. Central adiponectin signaling and an increase in leptin levels may evoke changes in sympathetic tone and HTN. The authors speculate whether decreased adiponectin signaling in the brain might cause HTN and whether adiponectin injections into the brain can lessen HTN. The authors address the role of adipose tissue innervation.

There is a bidirectional link between the brain and adipose tissue depots. Adipokines and the autonomic nervous system are involved in this link. Both the sympathetic and parasympathetic parts of the autonomic nervous system innervate adipose tissue. The sympathetic nervous system affects lipolysis, lipogenesis, adipocyte proliferation, thermogenesis, adipokine secretion, and noradrenaline production. Recent evidence suggests the parasympathetic nervous system functions as a glucose uptake regulator and free fatty acid metabolism inducer in adipose tissue. The authors discuss adipose tissue mass, quality, and location and how these factors are key to fine tuning the relationship between adiposity and blood pressure regulation. They mention a lack of pharmaceutical strategies to directly target adipose tissue and modulation of adipose tissue function and the use of alternative interventions including physical activity, diets, liposuction and pharmacological treatment to induce lipolysis or appetitesuppression. Briefly they discuss physical activity, diet, liposuction, and pharmaceutical approaches to modulate adipose tissue. They include information regarding beta3 receptor signaling as a promising target for treatment of obesity.

Although the authors are largely focused on HTN and CVD, the physiology and potential pathophysiology they present concerning adipose tissue and their speculations on how to affect this physiology are very valuable to an understanding of the disease of obesity in humans. It’s a deep dive but it’s worth an attempt. Then we can use some of this information to improve our care of people with the disease of obesity and to improve our attempts to understand the causes and possible prevention techniques

Article Review Author: Allen Browne, MD, FAAP, FACS, FOMA, DABOM

Galley JC, Singh S, Awata WMC, Alves JV, Bruder-Nascimento T. Adipokines: Deciphering the cardiovascular signature of adipose tissue. Biochem Pharmacol. 2022;206:115324. doi:10.1016/j.bcp.2022.115324

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Article reviewed by:

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Dr Browne is a retired pediatric surgeon and pediatric obesity medicine physician. He now focuses on education about the disease of obesity and obesity as a disease and is an advocate for children with the disease of obesity and their families.