A Complex Disorder

Factors that likely contribute to obesity include disruptions to intercellular signaling, increased inflammation, and changes to the gut microbiome.
 

Nov 1, 2015
Stephen D. Hursting, Ciara H. O’Flanagan, Laura W. Bowers

© EVAN OTO/SCIENCE SOURCE

Some 20 percent of cancer-related deaths in the U.S. can be attributed to obesity, making it the number-one preventable cause of cancer death in the country. But with myriad metabolic and inflammatory changes associated with obesity, determining the mechanisms that underlie the obesity-cancer link has proven challenging.

 

 

 

 

 

 

 

 

 

 


Insulin Resistance                                      Cell Signaling

Many obese individuals are resistant to insulin, driving increased production of the hormone, which can promote cancer development and growth and confer resistance to certain chemotherapies. Disruptions to the signaling pathways that mediate communication between neighboring or distant cells may promote tumor development and/or progression.

 


Active Adipocytes                                        Inflammation

Adipocytes in the tumor microenvironment are more active in obese patients and secrete various cancer-promoting hormones and cytokines. Metabolic changes associated with obesity can stimulate macrophages to produce excess amounts of proinflammatory compounds that promote cancer development and/or progression by causing DNA damage, inhibiting apoptosis, and stimulating cell migration and invasion.

 


Gut Microbiome                                          Endocrine Dysfunction

Obesity can lead to reduced gut bacterial diversity and impaired gut barrier function, allowing bacterial compounds such as lipopolysaccharide (LPS) to leak out of the intestine. This can further increase inflammation and perhaps promote cancer progression.

Obesity can increase aromatase expression, resulting in increased estradiol levels, which can promote the growth of estrogen-dependent cancers, including estrogen receptor– positive breast cancers and endometrial cancers.

 

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