cholecystokinin and Hypertriglyceridemia

Little is known about the effect of dietary fat emulsion microstructure on plasma TG concentrations, satiety hormones, and food intake. The aim of this study was to structure dietary fat to slow digestion and flatten postprandial plasma TG concentrations but not increase food intake. Emulsions were stabilized by egg lecithin (control), sodium sterol lactylate, or sodium caseinate/monoglyceride (CasMag) with either liquid oil or a liquid oil/solid fat mixture. In a randomized, double-blind, crossover design, 4 emulsions containing 30 g of fat in a 350-mL preload were consumed by 10 men and 10 women (BMI = 25.1 ± 2.8 kg/m(2); age = 58.8 ± 4.8 y). Pre- and postprandial plasma TG, cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), and peptide YY (PYY) concentrations and food intake were measured. In a second experiment in a subset of the participants (n = 8, 4 men and 4 women), (13)C-labeled mixed TG was incorporated into 2 different emulsions and breath (13)C was measured over 6 h. In the first experiment, the postprandial rise in plasma TG concentrations following the CasMag-stabilized emulsion containing 30% solid fat was lower than all other emulsions at 90 and 120 min (P < 0.05). Plasma CCK (P < 0.0001), GLP-1 (P < 0.01), and PYY (P < 0.001) concentrations were also reduced following this emulsion compared with control. Food intake at a test meal, eaten 3 h after the preload, did not differ among the emulsions. In the second experiment, when measured by the (13)C breath test, 25% of the TG in the CasMag emulsion was absorbed and metabolized compared with control. In conclusion, fat can be structured to decrease its effect on plasma TG concentrations without increasing food intake.

Topics: Breath Tests; Cholecystokinin; Cross-Over Studies; Dietary Fats; Digestion; Double-Blind Method; Emulsifying Agents; Emulsions; Energy Intake; Female; Glucagon-Like Peptide 1; Humans; Hypertriglyceridemia; Intestinal Absorption; Kinetics; Male; Middle Aged; Peptide YY; Satiation; Triglycerides

The aim of this study was to unravel the mechanisms responsible for the increased risk of gall stone disease in hypertriglyceridaemia (HTG) and to compare the effects of triglyceride lowering therapy by bezafibrate and fish oil on determinants of cholelithiasis (biliary lipid composition and gall bladder motility) in HTG patients.. Gall bladder motility (ultrasonography) was studied postprandially and during infusion of cholecystokinin (CCK). Determinants of cholelithiasis and serum lipids were compared between nine HTG patients and 10 age, sex, and body mass index matched normolipidaemic controls. The effects of bezafibrate and fish oil in HTG patients were studied in a randomised cross over trial.. HTG patients showed 14-fold higher serum triglyceride (TG) levels than controls. Biliary lipid composition, fasting gall bladder volumes, and CCK levels did not differ between HTG patients and controls. Gall bladder emptying was reduced in HTG patients compared with controls during CCK infusion (-22%) as well as in response to a meal (-37%; both p<0.001). Postprandial CCK levels were significantly higher in HTG patients. Both bezafibrate and fish oil reduced serum TG levels (-68% and -51% v baseline, respectively; both p<0.01). Fasting CCK levels were not affected whereas CCK induced gall bladder emptying increased during bezafibrate (+29%; p<0.001) and tended to increase on fish oil therapy (+13%; p=0.07). Postprandial gall bladder motility improved on bezafibrate and fish oil (+47 and +25% v baseline, respectively; both p<0.02) at least partly due to increased gall bladder sensitivity to CCK (both p<0.05 v baseline). Bezafibrate but not fish oil increased the molar ratio of cholesterol to bile acids (+40%; p

Topics: Analysis of Variance; Bezafibrate; Bile; Case-Control Studies; Cholecystokinin; Cholelithiasis; Cholesterol; Cross-Over Studies; Fish Oils; Gallbladder; Gallbladder Emptying; Humans; Hypertriglyceridemia; Hypolipidemic Agents; Lipids; Male; Risk; Statistics, Nonparametric; Ultrasonography

Cholecystokinin (CCK) is a peptide hormone that induces bile release into the intestinal lumen which in turn aids in fat digestion and absorption in the intestine. While excretion of bile acids and cholesterol into the feces eliminates cholesterol from the body, this report examined the effect of CCK on increasing plasma cholesterol and triglycerides in mice. Our data demonstrated that intravenous injection of [Thr28, Nle31]-CCK at a dose of 50 ng/kg significantly increased plasma triglyceride and cholesterol levels by 22 and 31%, respectively, in fasting low-density lipoprotein receptor knockout (LDLR(-/-)) mice. The same dose of [Thr28, Nle31]-CCK induced 6 and 13% increases in plasma triglyceride and cholesterol, respectively, in wild-type mice. However, these particular before and after CCK treatment values did not achieve statistical significance. Oral feeding of olive oil further elevated plasma triglycerides, but did not alter plasma cholesterol levels in CCK-treated mice. The increased plasma cholesterol in CCK-treated mice was distributed in very-low, low and high density lipoproteins (VLDL, LDL and HDL) with less of an increase in HDL. Correspondingly, the plasma apolipoprotein (apo) B48, B100, apoE and apoAI levels were significantly higher in the CCK-treated mice than in untreated control mice. Ligation of the bile duct, blocking CCK receptors with proglumide or inhibition of Niemann-Pick C1 Like 1 transporter with ezetimibe reduced the hypercholesterolemic effect of [Thr28, Nle31]-CCK in LDLR(-/-) mice. These findings suggest that CCK-increased plasma cholesterol and triglycerides as a result of the reabsorption of biliary lipids from the intestine.

Topics: Animals; Apolipoproteins; Blotting, Western; Cholagogues and Choleretics; Cholecystokinin; Cholesterol; Enzyme-Linked Immunosorbent Assay; Hypertriglyceridemia; Intestinal Mucosa; Lipids; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Receptors, LDL; Triglycerides