Influence of the Ketogenic Diet on Quality of Life in Patients Through the Inhibition of Oncogenic Signaling Pathways and Insulin Receptors in Tumors

mitigate HFD-induced disruptions in mucosal barrier function in the context of pancreatic carcinogenesis.Methods: Male and female KC mice (N7-13) were weaned at 5 weeks of age and fed a low-fat control diet (CD; 10.5% fat) or a high-fat diet (HFD; 60% fat) for 21 weeks.To assess the effects of a dietary switch from a HFD to a low-fat diet, a subset of mice were fed the HFD for 8 weeks, then switched to a CD for 13 weeks.At 26 weeks of age, all mice were euthanized and various tissues were collected.Results: Consumption of a HFD for 21 weeks led to: i) an increase in body weight; ii) disruption of tight junction structure (ZO-1 and occludin); iii) activation of proinflammatory cascades (NF-B) downstream the TLR4 receptor; iv) and increased MMP-2 and MMP-9 activity.These effects were mitigated by switching mice from a HFD to a CD.In male mice, the dietary switch prevented HFD-induced decreases in the number of goblet cells (GC) per crypt.Consumption of the HFD led to a reduction in colonic mRNA levels of Klf4, a transcription factor involved in GC terminal differentiation, which was not reverted by the dietary intervention.A similar trend was observed in the expression of GC-produced Tff3.Overall, there was a lower incidence of pancreatic cancer in the dietary switch group (0/17; 0%) in comparison to the HFD group (2/21; 10%).Conclusions: Our preliminary findings suggest that consumption of the HFD compromised mucosal barrier function and integrity in mice, which can be partially reversed by switching from a HFD to a CD.