Linoleic acid and butyrate synergize to increase Bcl-2 levels in colonocytes.
The biological properties of polyunsaturated fatty acid (PUFA) classes have been the source of much contention. For example, n-3 PUFA are chemoprotective, whereas n-6 PUFA may promote tumor development. Since dietary components can have combinatorial effects, we further examined the apoptotic properties of n-3 or n-6 fatty acids when combined with different fiber sources. Mice were fed diets supplemented with either fish oil (FO; enriched in n-3 PUFA) or corn oil (CO; enriched in n-6 PUFA) and nonfermentable (cellulose) or fermentable (pectin) fiber sources. In complementary experiments, immortalized young adult mouse colonic (YAMC) cells were treated with docosahexaenoic acid (DHA; 22:6n-3) or linoleic acid (LA; 18:2n-6) with or without butyrate. Mice fed a FO and pectin diet had significantly (p < 0.05) increased levels of apoptosis in colonocytes compared to all other diets. Similarly, apoptosis was highly induced in DHA and butyrate cotreated YAMC cells. In contrast, in both YAMC and mouse models, LA/CO with butyrate/pectin treatment reduced apoptosis and enhanced expression of bcl-2. The LA and butyrate induced antiapoptotic phenotype was reversed by knocking down bcl-2 using targeted siRNA. In comparison, overexpression of bcl-2 blocked the proapoptotic effect of DHA and butyrate. These data provide new mechanistic insights into the regulation of apoptosis by dietary PUFA and fiber.
Turk
Harmony F
HF
Program in Integrative Nutrition and Complex Diseases, Texas A&M University, College Station, TX, USA.
Kolar
Satya S
SS
Fan
Yang-Yi
YY
Cozby
Caitlin A
CA
Lupton
Joanne R
JR
Chapkin
Robert S
RS
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002087:Butyrates / Q000008:administration & dosage / Q000494:pharmacology*; D002478:Cells, Cultured; D002482:Cellulose / Q000008:administration & dosage / Q000494:pharmacology; D003106:Colon / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D003314:Corn Oil / Q000008:administration & dosage / Q000494:pharmacology; D004281:Docosahexaenoic Acids / Q000494:pharmacology; D004357:Drug Synergism; D005395:Fish Oils / Q000008:administration & dosage / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D015151:Immunoblotting; D020287:In Situ Nick-End Labeling; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D019787:Linoleic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010368:Pectins / Q000008:administration & dosage / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction
D002087:Butyrates; D005395:Fish Oils; D019253:Proto-Oncogene Proteins c-bcl-2; D004281:Docosahexaenoic Acids; D003314:Corn Oil; D010368:Pectins; D002482:Cellulose; D019787:Linoleic Acid