Do Gut Hormones Play a Role in Obesity Related Cancers?

Obesity is now well recognised as an important risk factor for cancers of the GI tract including oesophagus, stomach, colon, gall-bladder, liver, and pancreas. Furthermore, weight-loss interventions, particularly bariatric surgery, have been shown to reduce cancer morbidity and mortality in people living with obesity.

Traditionally, obesity related cancer risk has been attributed partly to dietary patterns associated with obesity, as well as insulin resistance (with hyperinsulinemia), increased production of pro-inflammatory cytokines, and changes in sex hormones. 

Now, a review paper by Maria Angela Guzzardi and colleagues, published in the International Journal of Obesity, discusses the possibility that obesity related alterations in gut hormones may play a hitherto unrecognised role in the etiology of these cancers. 

Gut hormones play a vital role in a wide range of processes ranging from local influences on GI motility, exocrine function and the bacteriome to systemic influences on appetite, glucose homeostasis, and immune response. 

As an example, the authors discuss the role of GLP-1:

“Recent studies have shown that GLP-1 receptor (GLP-1R) agonists might have a beneficial anti-inflammatory role independent from the glycemic regulatory actions. In fact, GLP-1R agonists modulate enteric immune response by activating intestinal intraepithelial lymphocytes GLP1R, which may influence microbiota composition and intestinal inflammation. Therefore, the blunted GLP-1 secretion in obesity contributes to the obesity-related pro-inflammatory condition.”

Similarly, vasoactive intestinal peptide (VIP),

“…is a regulator of both innate and adaptive immunity, with an anti-inflammatory role. In fact, in innate immune cells, VIP can inhibit the production of pro-inflammatory factors (e.g., TNF-alpha, IL-6, IL1beta, IL12, iNOS) and promote the production of anti-inflammatory factors (e.g., IL-10 and TGF-beta). In the adaptive immune system, VIP shifts the Th1/Th2 balance during CD4 T cell differentiation in favor of Th2 cells, both in vitro and in vivo, primarily through the vasoactive intestinal peptide receptor-2 (VPAC2).”

Based on the observation that neoplastic samples have been shown to express receptors for many gut hormones, the authors also discuss at length the evidence that gut hormones could modulate the proliferation and perhaps invasiveness of a wide range of cancers. 

However, they also note that,

“Overall, existing data are controversial, which might be due to differences between local and systemic effects of the hormone, and among cancer types.”

Hopefully this review will prompt further studies exploring the potential role of obesity-related alteration of gut hormones in the pathogenesis of specific tumors, which will open the perspective of new strategies in the prevention and treatment of cancer in patients with obesity.

@DrSharma
Berlin, D