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Title: DIETARY WHEY PROTEIN LOWERS SERUM C-PEPTIDE CONCENTRATION AND DUODENAL SREBP-1C MRNA ABUNDANCE, AND REDUCES OCCURRENCE OF DUODENAL TUMORS AND COLON ABERRANT CRYPT FOCI IN AZOXYMETHANE-TREATED MALE RATS

Author
item XIAO, RIJIN - ACNC
item CARTER, JULIA - ACNC
item LINZ, AMANDA - ACNC
item FERGUSON, MATTHEW - ACNC
item BADGER, THOMAS - ACNC/UAMS
item SIMMEN, FRANK - ACNC/UAMS

Submitted to: Journal of Nutritional Biochemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/16/2005
Publication Date: 9/15/2006
Citation: Xiao, R., Carter, J.A., Linz, A.L., Ferguson, M., Badger, T.M., Simmen, F.A. 2006. Dietary whey protein lowers serum C-peptide concentration and duodenal SREBP-1c mRNA abundance, and reduces occurrence of duodenal tumors and colon aberrant crypt foci in azoxymethane-treated male rats. Journal of Nutritional Biochemistry. 17(9):626-634.

Interpretive Summary: We examined the effect of feeding a whey protein mixture on subsequent tumor formation in the intestines of rats. Feeding whey protein to rats slowed the formation of tumors in small intestine and large intestine that were caused by a chemical agent referred to as azoxymethane. Feeding of whey protein also lowered insulin levels and this was correlated with dietary protection from tumors. Other of our data suggested an effect of whey protein to reduce the number of cancers that began the cancer process. Our data indicate potential beneficial effects of whey proteins in the diet for protection from developing colon and intestinal cancers.

Technical Abstract: We evaluated partially hydrolyzed whey protein (WPH) for inhibitory effects on the development of colon aberrant crypt foci (ACF) and intestinal tumors in azoxymethane (AOM)-treated rats. Pregnant Sprague–Dawley rats and their progeny were fed AIN-93G diets containing casein (CAS, control diet) or WPH as the sole protein source. Colons and small intestines from the male progeny were obtained at 6, 12, 20 and 23 weeks after AOM treatment. At 6 and 23 weeks, post-AOM, WPH-fed rats had fewer ACF than did CAS-fed rats. Intestinal tumors were most frequent at 23 weeks, post-AOM. At this time point, differences in colon tumor incidence with diet were not observed; however, WPH-fed rats had fewer tumors in the small intestine (7.6% vs. 26% incidence, P=.004). Partially hydrolized whey protein suppressed circulating C-peptide concentration (a stable indicator of steady-state insulin secretion) at all four time points relative to the corresponding CAS-fed animals. The relative mRNA abundance for the insulin-responsive, transcription factor gene, SREBP-1c, was reduced by WPH in the duodenum but not colon. Results indicate potential physiological linkages of dietary protein type with circulating C-peptide (and by inference insulin), local expression of SREBP-1c gene and propensity for small intestine tumorigenesis