The Role of Adipokines in Pancreatic Cancer

Abstract

In modern society, inappropriate diets and other lifestyle habits have made obesity an increasingly prominent health problem. Pancreatic cancer (PC), a kind of highly aggressive malignant tumor, is known as a silent assassin and is the seventh leading cause of cancer death worldwide, pushing modern medicine beyond help. Adipokines are coming into notice because of the role of the intermediate regulatory junctions between obesity and malignancy. This review summarizes the current evidence for the relationship between highly concerning adipokines and the pathogenesis of PC. Not only are classical adipokines such as leptin and adiponectin included, but they also cover the recognized chemerin and osteopontin. Through a summary of the biological functions of these adipokines as well as their receptors, it was discovered that in addition to their basic function of stimulating the biological activity of tumors, more studies confirm that adipokines intervene in the progression of PC from the viewpoint of tumor metabolism, immune escape, and reprogramming of the tumor microenvironment (TME). Besides endocrine function, the impact of white adipose tissue (WAT)-induced chronic inflammation on PC is briefly discussed. Furthermore, the potential implication of the acknowledged endocrine behavior of brown adipose tissue (BAT) in relation to carcinogenesis is also explored. No matter the broad spectrum of obesity and the poor prognosis of PC, supplemental research is needed to unravel the detailed network of adipokines associated with PC. Exploiting profound therapeutic strategies that target adipokines and their receptors may go some way to improving the current worrying prognosis of PC patients.

Strengthening the Evidence for a Causal Link between Type 2 Diabetes Mellitus and Pancreatic Cancer: Insights from Two-Sample and Multivariable Mendelian Randomization

“…The pathophysiological mechanisms linking T2DM to PaCa are complex and multifaceted, encompassing insulin resistance and hyperinsulinemia [16,[36][37][38], persistent hyperglycemia [39][40][41][42], chronic inflammation [16,43,44], alterations in gut microbiota [45][46][47][48][49], and dysregulated adipokine secretion [16,[50][51][52][53][54]. Insulin resistance in T2DM leads to hyperinsulinemia, potentially promoting tumor growth directly by acting on insulin receptors or indirectly by increasing levels of insulin-like growth factor-1 (IGF-1), both of which can stimulate cell proliferation and inhibit apoptosis to enhance cell proliferation pathways [36][37][38].…”

“…Changes in the gut microbiota related to T2DM may influence systemic inflammation and metabolic profiles, which may affect cancer development through alterations in bile acid metabolism and the release of metabolites that may have carcinogenic properties [45][46][47][48][49]. Moreover, altered adipokine secretion, characterized by increased leptin and decreased adiponectin levels due to adiposity in T2DM, may facilitate cancer progression through pro-inflammatory and anti-apoptotic effects [50][51][52][53][54]. These interconnected pathways underscore the complex relationship between T2DM and PaCa.…”

Assessment of the Role of Leptin and Adiponectinas Biomarkers in Pancreatic Neuroendocrine Neoplasms

“…Intraductal papillary mucinous neoplasm (IPMN) dysplastic grade, which can progress to pancreatic cancer, correlates with circulating leptin levels [ 76 ]. While leptin enhances pancreatic cancer progression through different signaling pathways, adiponectin may exert a protective effect that is rarely observed with other adipokines [ 77 ]. The phosphatidylinositol 3-kinase/protein kinase B(PI3K/AKT) signaling pathway is an important mediator in the development and migration of pancreatic cancer associated with obesity and plays a key role in pancreatic cancer cell proliferation and metastasis [ 78 ].…”

Genome, Metabolism, or Immunity: Which Is the Primary Decider of Pancreatic Cancer Fate through Non-Apoptotic Cell Death?

“…PDAC-related diabetes can be differentiated from type II diabetes through the measurement of both Adiponectin (a hormone secreted by adipocytes) and the interleukin-1 receptor antagonist (IL-1Ra) [180]. Adiponectin (APN) is an anti-tumor and anti-angiogenesis agent that inversely correlates with pancreatic cancer [174,175]. As a result of increasing mitochondrial Ca 2+ levels, which produce superoxide and, subsequently, activate RIPK1, pancreatic cancer cells undergo necroptosis in response to agonists of the APN receptor (AdipoRon).…”