Calcium reduces the increased fecal 1,2-sn-diacylglycerol content in intestinal bypass patients: a possible mechanism for altering colonic hyperproliferation.
Diacylglycerol (DAG) is a second messenger for protein kinase C, an enzyme with a key role in cellular signal transduction and growth control. In previous studies, it was demonstrated that DAG is produced by intestinal microflora. Bacterial DAG production is increased by bile acids and phospholipids, both of which may be precipitated by calcium. We have demonstrated that fecal total lipids, bile acids, and rectal epithelial proliferation are increased in intestinal bypass (IB) patients. Calcium was shown to alter fecal lipid composition and to reduce cell proliferation. In the present study, fecal DAG content and 14C-labeled DAG, 14C-phosphatidylcholine, and 14C-phosphatidylinositol metabolism were measured in 24-h stool collections in 15 stable IB patients before and after 3-month therapy with oral elemental calcium, 2.4 or 3.6 g/day. Fecal DAG concentration and output in IB patients were > 25- and > 200-fold greater than in normal controls. Oral calcium markedly reduced fecal DAG concentration and output and increased DAG, phosphatidylcholine, and phosphatidylinositol metabolism without enhancing DAG production. We conclude that fecal DAG content is markedly elevated post-IB and that calcium supplementation in these patients reduces fecal DAG and accelerates bacterial metabolism of DAG and its precursors. In separate studies, we have found that calcium supplementation also decreases rectal hyperproliferation in IB patients. Taken together, these findings suggest that a high luminal level of DAG enhances colonic cell proliferation and that calcium reduces cell proliferation in part by decreasing the level of DAG.
Steinbach
G
G
Department of Medicine, St. Luke's/Roosevelt Hospital Center, New York, New York 10025.
Morotomi
M
M
Nomoto
K
K
Lupton
J
J
Weinstein
I B
IB
Holt
P R
PR
D002118:Calcium / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D003106:Colon / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D004075:Diglycerides / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005243:Feces / Q000737:chemistry* / Q000382:microbiology; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007581:Jejunoileal Bypass; D009765:Obesity / Q000601:surgery; D010713:Phosphatidylcholines / Q000378:metabolism; D012007:Rectum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
C011439:1,2-diacylglycerol; D004075:Diglycerides; D005230:Fatty Acids, Nonesterified; D010713:Phosphatidylcholines; D002118:Calcium