The Adipocyte-Macrophage Relationship in Cancer: A Potential Target for Antioxidant Therapy

Obesity has emerged as a major public health concern with a staggering 39% worldwide prevalence as of 2021. Given the magnitude of the problem and considering its association with chronic low-grade systemic inflammation, it does not come as a surprise that obesity is now considered one of the major risk factors for the development of several chronic diseases, such as diabetes, cardiovascular problems, and cancer. Adipose tissue dysfunction in obesity has taken center stage in understanding how changes in its components, particularly adipocytes and macrophages, participate in such processes. In this review, we will initially focus on how changes in adipose tissue upon excess fat accumulation generate endocrine signals that promote cancer development. Moreover, the tumor microenvironment or stroma, which is also critical in cancer development, contains macrophages and adipocytes, which, in reciprocal paracrine communication with cancer cells, generate relevant signals. We will discuss how paracrine signaling in the tumor microenvironment between cancer cells, macrophages, and adipocytes favors cancer development and progression. Finally, as reactive oxygen species participate in many of these signaling pathways, we will summarize the information available on how antioxidants can limit the effects of endocrine and paracrine signaling due to dysfunctional adipose tissue components in obesity.

Automated summary

Obesity, with a worldwide prevalence of 39% as of 2021, is a major public health concern. It is strongly associated with chronic low-grade systemic inflammation and has become a significant risk factor for the development of various chronic diseases, such as diabetes, cardiovascular problems, and cancer. Dysfunctional components in adipose tissue, particularly adipocytes and macrophages, play a central role in understanding how obesity leads to these diseases. This review focuses on the endocrine signals generated by excess fat accumulation in adipose tissue that promote cancer development, as well as the paracrine communication between cancer cells, macrophages, and adipocytes in the tumor microenvironment that supports cancer progression. Additionally, the involvement of reactive oxygen species in these signaling pathways and the potential of antioxidants to mitigate the effects of dysfunctional adipose tissue in obesity will be discussed.