Insight on the Role of Leptin: A Bridge from Obesity to Breast Cancer

Abstract

Leptin is a peptide hormone, mainly known for its role as a mediator of adipose tissue endocrine functions, such as appetite control and energy homeostasis. In addition, leptin signaling is involved in several physiological processes as modulation of innate and adaptive immune responses and regulation of sex hormone levels. When adipose tissue expands, an imbalance of adipokines secretion may occur and increasing leptin levels contribute to promoting a chronic inflammatory state, which is largely acknowledged as a hallmark of cancer. Indeed, upon binding its receptor (LEPR), leptin activates several oncogenic pathways, such as JAK/STAT, MAPK, and PI3K/AKT, and seems to affect cancer immune response by inducing a proinflammatory immune polarization and eventually enhancing T-cell exhaustion. In particular, obesity-associated hyperleptinemia has been related to breast cancer risk development, although the underlying mechanism is yet to be completely clarified and needs to be deemed in light of multiple variables, such as menopausal state and immune response. The aim of this review is to provide an overview of the potential role of leptin as a bridge between obesity and breast cancer and to establish the physio-pathological basis of the linkage between these major health concerns in order to identify appropriate and novel therapeutic strategies to adopt in daily clinical practice.