Leptin: A Heavyweight Player in Obesity-Related Cancers

Abstract

Obesity, defined as the abnormal or excessive expansion of white adipose tissue, has reached pandemic proportions and is recognized as an important health concern since it is a common root for several comorbidities, including malignancies. Indeed, the current knowledge of the white adipose tissue, which shifts its role from an energy storage tissue to an important endocrine and metabolic organ, has opened up new avenues for the discovery of obesity’s effects on tumor biology. In this review, we will report the epidemiological studies concerning the strong impact of obesity in several types of cancer and describe the mechanisms underlying the heterotypic signals between cancer cell lines and adipocytes, with particular emphasis on inflammation, the insulin/IGF-1 axis, and adipokines. Among the adipokines, we will further describe the in vitro, in vivo, and clinical data concerning the role of leptin, recognized as one of the most important mediators of obesity-associated cancers. In fact, leptin physiologically regulates energy metabolism, appetite, and reproduction, and several studies have also described the role of leptin in affecting cancer development and progression. Finally, we will summarize the newest pharmacological strategies aimed at mitigating the protumorigenic effects of leptin, underlining their mechanisms of action.

The role of leptin in regulation of the soluble amyloid precursor protein α (sAPPα) levels in lung cancer cell media

“…Leptin was shown to be upregulated in lung tumors compared with normal lung increasing their growth, proliferation, and metastasis, with anti-apoptotic functions 15 , 17 , 20 , 21 . A positive correlation was observed with increased malignancy of different cancer subtypes and leptin expression 15 – 17 , 20 , 24 .…”

The Potential Role of C-Reactive Protein in Metabolic-Dysfunction-Associated Fatty Liver Disease and Aging

“…The nomenclature of MASLD emphasizes the central role of metabolic dysfunction in the pathogenesis of fatty liver, in which CRP affects the regulation of fat metabolism by leptin, forming the first hit. Leptin is a 16 kDa pleiotropic peptide hormone encoded by the obesity (Ob) gene that acts by binding to the Ob receptor (ObR) to regulate appetite and energy expenditure [74]. Leptin limits triglyceride storage to prevent lipotoxicity, exerts antisteatogenic effects, and improves insulin sensitivity by inhibiting hepatic glucose production and lipogenesis [75].…”

Adipocyte Microenvironment in Ovarian Cancer: A Critical Contributor?

“…Conversely, several pieces of evidence have shown that leptin, whose circulating levels increase proportionally with fat mass, directly or indirectly affects the biology of several cancers. In summary, obesity has been recognized as a potential promoter of cancer growth through several mechanisms [69].…”