Adipose Tissue, Obesity and Adiponectin: Role in Endocrine Cancer Risk

Abstract

Adipose tissue has been recognized as a complex organ with endocrine and metabolic roles. The excess of fat mass, as occurs during overweight and obesity states, alters the regulation of adipose tissue, contributing to the development of obesity-related disorders. In this regard, many epidemiological studies shown an association between obesity and numerous types of malignancies, comprising those linked to the endocrine system (e.g., breast, endometrial, ovarian, thyroid and prostate cancers). Multiple factors may contribute to this phenomenon, such as hyperinsulinemia, dyslipidemia, oxidative stress, inflammation, abnormal adipokines secretion and metabolism. Among adipokines, growing interest has been placed in recent years on adiponectin (APN) and on its role in carcinogenesis. APN is secreted by adipose tissue and exerts both anti-inflammatory and anti-proliferative actions. It has been demonstrated that APN is drastically decreased in obese individuals and that it can play a crucial role in tumor growth. Although literature data on the impact of APN on carcinogenesis are sometimes conflicting, the most accredited hypothesis is that it has a protective action, preventing cancer development and progression. The aim of the present review is to summarize the currently available evidence on the involvement of APN and its signaling in the etiology of cancer, focusing on endocrine malignancies.

Keywords: adiponectin; adipose tissue; endocrine cancer; obesity.

Figure 1

APN’s molecular structure and isoforms. Monomeric APN is able to trimerize to form low molecular weight (LMW) APN. Two trimers can then combine to form middle molecular weight (MMW) hexamers. The trimers are able to form 12- or 18-mers with high molecular weight (HMW).

Figure 2

APN’s receptor-mediated and paracrine actions on endocrine cancer cells. (A) APN activates adenosine monophosphate-activated protein kinase (AMPK) via an increased expression of the adaptor protein APPL-1 as well as the Ser/Thr kinase LKB1. AMPK activation affects cell growth by inducing p53, p21 and phosphatase 2A (PP2A) expression. Down-regulation of the mammalian target of rapamycin (mTOR), PI3K/Akt and Cyclin D1 signaling is also implicated in the APN-mediated growth arrest and apoptosis; (B) In adipocytes, APN inhibits aromatase activity, lowering estrogen production and reducing ERα-stimulation in adjacent breast cancer cells. It negatively affects pro-survival pathways.