Obesity-Associated Cancers: Evidence from Studies in Mouse Models

Abstract

Obesity, one of the major problems in modern human society, is correlated with various diseases, including type 2 diabetes mellitus (T2DM). In particular, epidemiological and experimental evidence indicates that obesity is closely linked to at least 13 different types of cancer. The mechanisms that potentially explain the link between obesity and cancer include hyperactivation of the IGF pathway, metabolic dysregulation, dysfunctional angiogenesis, chronic inflammation, and interaction between pro-inflammatory cytokines, endocrine hormones, and adipokines. However, how the largely uniform morbidity of obesity leads to different types of cancer still needs to be investigated. To study the link between obesity and cancer, researchers have commonly used preclinical animal models, particularly mouse models. These models include monogenic models of obesity (e.g., ob/ob and db/db mice) and genetically modified mouse models of human cancers (e.g., Kras-driven pancreatic cancer, Apc-mutated colorectal cancer, and Her2/neu-overexpressing breast cancer). The experimental results obtained using these mouse models revealed strong evidence of a link between obesity and cancer and suggested their underlying mechanisms.

Factors Associated with the Nutritional Status of Women with Non-Metastatic Breast Cancer in a Brazilian High Complexity Oncology Center

“…To gain a deeper understanding of this association [33], one hypothesis proposes that an elevated level of estrogen may be linked to the development of breast cancer, particularly in postmenopausal women [34]. Another possible hypothesis suggests that obesity contributes to the increased circulating insulin and insulin-like growth factor 1 (IGF-1), which, in turn, can promote cell proliferation and tumor growth [35]. Numerous epidemiological studies support the correlation between overweight and obese individuals and an elevated risk of cancer [36,37].…”

Hepatocyte-specific loss of DDB1 attenuates hepatic steatosis but aggravates liver inflammation and fibrosis in MASH

“…We further measured the expression of DDB1 in db/db and db/m mice, which are common monogenic obesity animals with fatty livers and their corresponding controls. [17] Distinct downregulation of DDB1 expression (Figure 1D, Supplemental Figure S1H, http://links.lww.com/HC9/ A940) was consistently detected in db/db mouse livers. In addition, we examined the expression of DDB1 in normal and MASH human livers.…”

The Ketogenic Diet Intervention in Obesity-Associated Colon Cancer Risk Reduction

“…A ketogenic diet has been shown to have a tumor growth-limiting effect to protect healthy cells from DNA damage and accelerates a promising opportunity for colon cancer cells toward chemotherapeutic toxicity or radiation [20,21]. Overall ketogenic diet metabolome during tumorigenesis in colon cancer.…”