## 1 Introduction  
Adipose tissue is specialized in fat storage and its function requires an extraordinary capacity of adapting to endogenous and systemic stimuli by metabolic reprogramming [1]. The metabolic failure leads to adipocyte imbalance; in particular, the disturbed mitochondrial activity causes metabolic stress, inflammation and increased production of ROS [2]. Obesity, which is the most evident manifestation of adipose tissue strain, is associated with a decreased mitochondrial content and oxidative capacity, suggesting that mitochondrial impairment may contribute to adipocyte dysfunction [3, 4]. Accumulating evidence indicates that obesity causes chronic low-grade inflammation, therefore contributing to systemic metabolic dysfunction associated with obesity-linked disorders [5]. Adipose tissue acts as a key endocrine organ by releasing adipokines with pro- or anti-inflammatory activities [6]. Among these molecules, TGF\(\beta\) is produced predominantly in pathological visceral adipose tissue. Indeed, locally within adipose tissues, different types of cells, including adipocytes, adipose progenitors, preadipocytes, resident endothelial cells and macrophages, produce proteins of the TGF\(\beta\) superfamily and their antagonists, creating a local microenvironment particularly sensitive to TGF\(\beta\) signaling [7]. Several studies have investigated the potential contribution of altered TGF\(\beta\) expression to adipose tissue dysfunction in mouse and human models of obesity, since the circulating levels of TGF\(\beta\) are increased in the adipose tissue of overweight and obese subjects compared to those of normal weight, highlighting a close association between TGF\(\beta\) levels and the increased body mass index during morbid obesity [8; 9; 10; 11]. Excess visceral adipose tissue induces a state of chronic systemic inflammation and altered metabolic activity that promotes a pro-oncogenic environment [12; 13]. Indeed, altered systemic release of adipokines, growth factors, and cytokines by dysfunctional adipose tissue in the overweight and obese is considered among the main players in malignant initiation and progression; the negative impact of dysfunctional adipose tissue has been described in pancreatic cancer [14; 15]. Epidemiological studies have suggested that overweight and obesity were associated with a greater risk of pancreatic cancer at a younger age of disease onset [16], whereas obesity at an older age was associated with a lower overall survival in patients with pancreatic cancer [17]. However, it remains to be elucidated how interactions between adipose tissue and tumor cells may influence the local invasion and metastasis of pancreatic ductal adenocarcinoma (PDAC), the most common subtype of this cancer in which patients present locally advanced or metastatic disease at the time of diagnosis [18]. In this scenario, TGF\(\beta\) could be considered one of the systemic mediators of the effects of dysfunctional and inflamed adipose tissue on pancreatic cancer cells. TGF\(\beta\) acts through the activation of the resident fibroblasts, and promotes the epithelial-mesenchymal transition (EMT) and the production of extracellular matrix (ECM) structural proteins (e.g., fibrous collagen and elastin) and adhesive proteins (e.g., laminin and fibronectin) [19]. In cancer, this pleiotropic cytokine contributes to the formation of the fibrotic tumor microenvironment promoting angiogenesis, immunosuppression, invasiveness and thereby metastasis [20]. Although the involvement of TGF\(\beta\) in pancreatic cancer makes the cytokine an interesting therapeutic target, the attempted preclinical and clinical investigations have shown that the pharmacological approach remains a clinical challenge [21]. The mechanisms underlying the obesity-cancer link are likely multifactorial, including metabolic and inflammation perturbations [22].