The role of long chain fatty acids in regulating food intake and cholecystokinin release in humans

Background and aims-The mechanism of intraduodenal fat induced inhibition o f food intake is still unclear. Therefore, we rested the ability of duodena l fatty acids to suppress food intake at a lunchtime meal; in addition, we were interested to test if these effects were mediated by cholecystokinin ( CCK) A receptors. Subjects and methods-Three sequential double blind, three period crossover studies were performed in 12 healthy males each: (1) subjects received intr aduodenal fat with or without 120 mg of tetrahydrolipstatin, an inhibitor o f gastrointestinal lipases, or saline; (2) volunteers received intraduodena l long chain fatty acids, medium chain fatty acids, or saline; (3) subjects received long chain fatty acids or saline together with concomitant intrav enous infusions of saline or loxiglumide, a specific CCK-A receptor antagon ist. The effect of these treatments on food intake and feelings of hunger w as quantified. Results-Intraduodenal fat perfusion significantly (p<0.05) reduced calorie intake. Inhibition of fat hydrolysis abolished this effect. Only long chain fatty acids significantly (p<0.05) decreased calorie intake, whereas mediu m chain fatty acids were ineffective. Infusion of loxiglumide abolished the effect of long chain fatty acids. Conclusions-Generation of long chain fatty acids through hydrolysis of fat is a critical step for fat induced inhibition of food intake; the signal is mediated via CCK-A receptors.