Obesity and colon cancer

Scientists have explained the mechanism of cancer development in obesity

Oleg Lischuk, N+1

American researchers have found out how obesity caused by excessive consumption of fatty foods contributes to the development of colon cancer. The results of the study are published in Nature (Beyaz et al., High-fat diet enhances stemness and tumorigenicity of intestinal progenitors).

In the course of the work carried out under the guidance of employees of Harvard University and the Massachusetts Institute of Technology, scientists fed mice high-calorie foods with 60 percent fat content for 9-14 months, which led to obesity. After that, Lgr5+ intestinal stem cells (KSCS) were studied in them, from which precancerous adenomatous lesions caused by suppression of the antitumor Apc gene originate.

To determine the number of CSCs, scientists carried out their in situ hybridization using the marker olfactomedin 4. It turned out that fatty foods increase the number of these cells by 50 percent and increase their regenerative activity compared to mice on a balanced diet. Moreover, this takes place due to a decrease in the intensity of cell differentiation, since the length of the intestinal villi decreases at the same time. The results obtained were confirmed in vitro (by growing intestinal organoids in 3D culture) and in vivo (by clonogenic research).

To identify the biochemical mechanism of such action, scientists sequenced matrix RNAs in isolated CSCs and progenitor cells of mice. It turned out that fatty foods significantly increase the level of transcription targets and binding sites of receptors activated by the proliferator peroxisome, type delta (PPAR-δ), which are important regulators of metabolism.

When normal-weight mice were prescribed the synthetic stimulator PPAR-δ GW501516 for four weeks, changes similar to the effects of fatty foods were observed in their intestines. A similar pattern was observed when treating intestinal organoids with purified fatty acids.

The data obtained indicate that the carcinogenic effect of fatty foods is associated with the activation of PPAR-δ receptors in stem and progenitor cells, which leads to an increase in their proliferation. Whether such a mechanism is involved in the development of tumors in obesity, not associated with increased consumption of fatty foods, remains to be seen.

Portal "Eternal youth" http://vechnayamolodost.ru  09.03.2016