TY - JOUR
T1 - Dietary fat and fiber interactively modulate apoptosis and mitochondrial bioenergetic profiles in mouse colon in a site-specific manner
AU - Fan, Yang-Yi
AU - Vaz, Frederic M.
AU - Chapkin, Robert S.
PY - 2017
Y1 - 2017
N2 - We have demonstrated that the combination of bioactive components generated by fish oil (containing n-3 polyunsaturated fatty acids) and fermentable fiber (leading to butyrate production) act coordinately to protect against colon cancer. This is, in part, the result of an enhancement of apoptosis at the base of the crypt across all stages (initiation, promotion, and progression) of colon tumorigenesis. As mitochondria are key organelles capable of regulating the intrinsic apoptotic pathway and mediating programmed cell death, we investigated the effects of diet on mitochondrial function by measuring mucosal cardiolipin composition, mitochondrial respiratory parameters, and apoptosis in isolated crypts from the proximal and distal colon. C57BL/6 mice (n= 15/treatment) were fed one of two dietary fats (corn oil and fish oil) and two fibers (pectin and cellulose) for 4 weeks in a 2x2 factorial design. In general, diet modulated apoptosis and the mucosal bioenergetic profiles in a site-specific manner. The fish/pectin diet promoted a more proapoptotic phenotype-for example, increased proton leak (Pinteraction= 0.002) compared with corn/cellulose (control) only in the proximal colon. With respect to the composition of cardiolipin, a unique phospholipid localized to the mitochondrial inner membrane where it mediates energy metabolism, fish oil feeding indirectly influenced its molecular species with a combined carbon number of C68 or greater, suggesting compensatory regulation. These data indicate that dietary fat and fiber can interactively modulate the mitochondrial metabolic profile and thereby potentially modulate apoptosis and subsequent colon cancer risk. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved
AB - We have demonstrated that the combination of bioactive components generated by fish oil (containing n-3 polyunsaturated fatty acids) and fermentable fiber (leading to butyrate production) act coordinately to protect against colon cancer. This is, in part, the result of an enhancement of apoptosis at the base of the crypt across all stages (initiation, promotion, and progression) of colon tumorigenesis. As mitochondria are key organelles capable of regulating the intrinsic apoptotic pathway and mediating programmed cell death, we investigated the effects of diet on mitochondrial function by measuring mucosal cardiolipin composition, mitochondrial respiratory parameters, and apoptosis in isolated crypts from the proximal and distal colon. C57BL/6 mice (n= 15/treatment) were fed one of two dietary fats (corn oil and fish oil) and two fibers (pectin and cellulose) for 4 weeks in a 2x2 factorial design. In general, diet modulated apoptosis and the mucosal bioenergetic profiles in a site-specific manner. The fish/pectin diet promoted a more proapoptotic phenotype-for example, increased proton leak (Pinteraction= 0.002) compared with corn/cellulose (control) only in the proximal colon. With respect to the composition of cardiolipin, a unique phospholipid localized to the mitochondrial inner membrane where it mediates energy metabolism, fish oil feeding indirectly influenced its molecular species with a combined carbon number of C68 or greater, suggesting compensatory regulation. These data indicate that dietary fat and fiber can interactively modulate the mitochondrial metabolic profile and thereby potentially modulate apoptosis and subsequent colon cancer risk. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved
U2 - https://doi.org/10.1097/CEJ.0000000000000263
DO - https://doi.org/10.1097/CEJ.0000000000000263
M3 - Article
C2 - 27167153
SN - 0959-8278
VL - 26
SP - 301
EP - 308
JO - European Journal of Cancer Prevention
JF - European Journal of Cancer Prevention
IS - 4
ER -