Satiation in humans is modulated by fatty acid chain length

Abstract

Background/Aims The role of cholecystokinin (CCK) in satiety and gastric accommodation is unclear. Whilst exogenous CCK induces satiation in humans, a similar role for endogenous CCK has not been established. Paradoxically, exogenous CCK also relaxes the stomach, which should increase meal volume tolerated. Recent work has shown that intragastric infusion of dodecanoic acid (C12) induces the release of CCK in humans but isocaloric decanoic acid (C10) does not (McLaughlin 1999 Gastroenterology 116:46). We therefore aimed to determine whether 1) intragastric C12 and C10 have differential effects on satiation to an intragastric water load, and 2) any differential effect is paralleled by changes in gastric tone. Methods Vehicle (0.251 PBS and 1.5% v/v Tween 80) alone or with 0.1M C10 or C12 were infused in randomized order into the stomach of 15 healthy volunteers (4 females; mean age 34, range 22-55) following an overnight fast. Subjects were blinded to the nature of the infusion. 20 rains later, water was infused into the stomach at O.21/min to maximum volume tolerated. Plasma CCK concentrations were determined by RIA pre and 15 rains post fatty acid infusion. In 5 of the subjects, the effect of intragastric vehicle, C10 or C12 on proximal gastric tone was studied during distension of a bag sited in the fundus. Data are mean -+ SEM. Water intake was compared using 1-way repeated measures ANOVA followed by Student-NewmanKeuls post hoc test. Paired data were compared by Student t-test. Results C12 induced a rise in plasma CCK (mean plasma CCK concentration pre-C12:3.3 _+ 0.6 pM; post-C12:10,3 +_ 1.4 pM; p<O.05), whilst C10 did not (pre-ClO: 4.6 _+ 2.4pM; post C10:5.5 -+ 0.9pM; p = 0.8). Subjects tolerated significantly more water following vehicle (1636 -+ 178ml) than C10 (1346 -+ 163ml; P<O.05 vs vehicle) and following C10 than C12 (867 -+ 112ml; p<O.05 vs C10), Vehicle alone did not influence proximal gastric tone. C10 and C12 caused a similar reduction in tone (mean reduction following C10:2 -+ 0.47 mmHg; following C12:2 -+ 0.53 mmHg). Conclusions 1) Fatty acid reduces tolerance to water infusion, but also decreases gastric tone. 2) Water tolerance is lower after C12 (which releases CCK) than C10 (which does not). 3) Fatty acids trigger satiation through both CCK-dependent and CCK-indepandent pathways.