High fat diet risk factor for gingival Immunosuppression and cancer

Abstract

ObjectiveHigh fat diet leading to obesity has been associated with many diseases including cancer. We determined the effect of high fat diet and obesity in the phenotype and function of immune cell infiltrates within different tissues including gingival tissues of mice with wild type and targeted KRAS mutations in the pancreas.Experimental methodsConditional LSL‐KRASG12D and p48‐Cre or PDX‐1‐Cre mice were bred and their offsprings were used for the studies. Mice with both the KrasG12D and Cre allele were designated as mutant mice (KC). Mice with neither the KrasG12D nor the Cre allele were used as wildtype (WT). Mice were fed either a high fat, high calorie diet (HFCD) or a control diet (CD) for 4 to 6 months before they were used for experiments. NK cytotoxicity was determined by 51Cr release assay and cytokine secretion by ELISA.ResultsThe Following profiles were obtained for NK cell cytotoxicity and secretion of IFN‐g from NK cells purified from spleen of KC or WT mice fed either with CD or HFCD (WT(CD)>WT(HFCD)>KC(CD)>KC(HFCD). Immune cells from blood and pancreas exhibited similar pattern of cytotoxicity to those obtained from the spleen but inverse profile of IFN‐g and IL‐6 secretion (WT(CD)<WT(HFCD)<KC(CD)<KC(HFCD) was seen. Mice fed with HFCD when compared to CD had much less NK cells both in WT and KC mice in pancreas, adipose and gingiva.ConclusionMice fed with HFCD exhibited higher inflammatory index when compared to those fed with CD both in WT and KC mice. In addition, numbers and the cytotoxicity of NK cells were severely decreased in pancreas and gingiva of WT and KC mice fed with HFCD. High fat diet exacerbates the progression of neoplastic lesions in KC mice and could be responsible for the oral mucosa pathologies due to decrease function and numbers of key immune effectors.Support or Funding InformationP01 CA163200; PAPD and XO clubThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.