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.
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.
Xiao
Rijin
R
Arkansas Children's Nutrition Center, University of Arkansas for Medical Sciences, Little Rock, AR 72202, USA.
Carter
Julie A
JA
Linz
Amanda L
AL
Ferguson
Matthew
M
Badger
Thomas M
TM
Simmen
Frank A
FA
D000818:Animals; D001397:Azoxymethane; D002096:C-Peptide / Q000097:blood*; D002828:Choristoma; D003108:Colonic Diseases; D004044:Dietary Proteins / Q000494:pharmacology; D004379:Duodenal Neoplasms / Q000139:chemically induced; D008297:Male; D008894:Milk Proteins / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism*; D000067816:Whey Proteins
D002096:C-Peptide; D004044:Dietary Proteins; D008894:Milk Proteins; D051780:Sterol Regulatory Element Binding Protein 1; D000067816:Whey Proteins; D001397:Azoxymethane