Adiponectin and Thyroid Cancer: Insight into the Association between Adiponectin and Obesity

Yuanyuan Zhou, Ying Yang, Taicheng Zhou, Bai Li, Zhanjian Wang, Yuanyuan Zhou, Ying Yang, Taicheng Zhou, Bai Li, Zhanjian Wang

Abstract

In recent decades, the incidence and diagnosis of thyroid cancer have risen dramatically, and thyroid cancer has now become the most common endocrine cancer in the world. The onset of thyroid cancer is insidious, and its progression is slow and difficult to detect. Therefore, early prevention and treatment have important strategic significance. Moreover, an in-depth exploration of the pathogenesis of thyroid cancer is key to early prevention and treatment. Substantial evidence supports obesity as an independent risk factor for thyroid cancer. Adipose tissue dysfunction in the obese state is accompanied by dysregulation of a variety of adipocytokines. Adiponectin (APN) is one of the most pivotal adipocytokines, and its connection with obesity and obesity-related disease has gradually become a hot topic in research. Recently, the association between APN and thyroid cancer has received increasing attention. The purpose of this review is to systematically review previous studies, give prominence to APN, focus on the relationship between APN, obesity and thyroid cancer, and uncover the underlying pathogenic mechanisms.

Keywords: adiponectin; obesity; thyroid cancer.

Conflict of interest statement

Conflicts of Interest The authors declare that they have no competing interests.

copyright: © 2021 Zhou et al.

Figures

Figure 1.
Figure 1.
The anti-inflammatory properties of APN. APN exerts its anti-inflammatory properties in different cell types through mechanisms as follows. In adipocytes, a bi-directional regulation has been shown to exist between APN and pro-inflammatory factors, such as TNF-α, IL-6, and CRP. APN treated macrophages exhibited impaired function of phagocytic activity, suppressed foam cell transformation, negative regulation of NF-κB signaling, decreased expression of TNF-α or IL-6, and increased release of IL-10 and IL-1RA. In endothelial cells, APN can negatively regulate the expression of VCAM-1, E-selectin, ICAM-1, CRP, and IL-8, and suppress endothelial NF-κB activation and ROS production. The red arrow indicates promotion, and the blue arrow indicates inhibition. Abbreviations: APN adiponectin, TNF-α tumor necrosis factor-α, IL-6 interleukin-6, CRP C-reactive protein, NF-κB nuclear factor kappa-B, IL-10 interleukin-10, IL-1RA interleukin-1 receptor agonist, VCAM-1 vascular cell adhesion molecule 1, ICAM-1 intracellular adhesion molecule 1, IL-8 interleukin-8, ROS reactive oxygen species.
Figure 2.
Figure 2.
The possible mechanisms underlying obesity and thyroid cancer. Elevated serum TSH and other obesity-related comorbidities, including abnormal insulin resistance, chronic low degree inflammation, oxidative stress, abnormalities of the IGF system, and altered secretion of adipokines, could be the possible carcinogenic mechanism underlying obesity and thyroid cancer. Moreover, all of these factors may interplay with each other, forming a vicious cycle. Abbreviations: TSH thyroid-stimulating hormone, IGF insulin-like growth factor.
Figure 3.
Figure 3.
The directly and indirectly anti-cancer pathways of APN. Binding to AdipoR1/2, APN could initiate a series of directly anti-cancer pathways, including inhibition of PI3K/AKT, ERK1/2, Wnt/GSK3β/β-catenin, STAT3, USP2, and Bcl-2 signals; as well as activation of AMPK by LKB1, then up-regulates TSC2, p53/p21/p27 and promotes cell autophagy. Moreover, the tumorigenicity of the IGF axis has been confirmed to be partially through ERK and PI3K/AKT pathways, which are belonging to the downstream signaling of the APN. Since APN can increase insulin sensitivity, it is reasonable to believe that the complexity of the APN-related signaling network has been added by the possible indirect association between APN, insulin resistance, and the abnormal IGF system. The blue solid arrows and red solid arrows indicate inhibitory and stimulatory effects in the direct pathway, respectively. In turn, the blue dotted lines and red dotted lines indicate the inhibitory and stimulatory effects in the indirect pathway, respectively. Abbreviations: APN adiponectin, PI3K/AKT phosphatidylinositol 3-kinase/protein kinase B, ERK1/2 extracellular signal-regulated kinases 1 and 2 Wnt wingless-type protein, GSK3β glycogen synthase kinase 3β, STAT3 signal transducer and activator of transcription 3, USP2 ubiquitin-specific protease 2, AMPK 5’ adenosine monophosphate-activated protein kinase, LKB1 liver kinase B1, TSC2 tuberous sclerosis complex 2, IGF insulin-like growth factor.

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