Glucose and GLP-2 (Glucagon-Like Peptide-2) Mobilize Intestinal Triglyceride by Distinct Mechanisms.

OBJECTIVE: Dietary triglycerides are partially retained in the intestine within intracellular or extracellular compartments, which can be rapidly mobilized in response to several stimuli, including glucose and GLP-2 (glucagon-like peptide-2). To elucidate the mechanism of intestinal lipid mobilization, this study examined the patterns and time course of lymph flow and triglycerides after glucose and GLP-2 treatment in rats. Approach and Results: Lymph flow, triglyceride concentration, and triglyceride output were assessed in mesenteric lymph duct-cannulated rats in response to an intraduodenal (i.d.) lipid bolus followed 5 hours later by either (1) i.d. saline+intraperitoneal (i.p.) saline (placebo), (2) i.d. glucose plus i.p. saline, (3) i.d. saline+i.p. GLP-2, or (4) i.d. glucose+i.p. GLP-2. GLP-2 and glucose administered alone or in combination stimulated total triglyceride output to a similar extent, but the timing and pattern of stimulation differed markedly. Whereas GLP-2 rapidly increased lymph flow with no effect on lymph triglyceride concentration or triglyceride:apoB48 (apolipoprotein B48) ratio (a surrogate marker of chylomicron size) compared with placebo, glucose transiently decreased lymph flow followed by delayed stimulation of lymph flow and increased lymph triglyceride concentration and triglyceride:apoB48 ratio. CONCLUSIONS: Glucose and GLP-2 robustly enhanced intestinal triglyceride output in rats but with different effects on lymph flow, lymph triglyceride concentration, and chylomicron size. GLP-2 stimulated triglyceride output primarily by enhancing lymph flow with no effect on chylomicron size, whereas glucose mobilized intestinal triglycerides, stimulating secretion of larger chylomicrons. This suggests that these 2 stimuli mobilize intestinal lipid by different mechanisms.

The postprandial situation as a pro-inflammatory condition / La situación posprandial como condición proinflamatoria

Postprandial lipemia has been associated with cardiovascular disease. The current pathophysiological concept is that postprandial remnant lipoproteins migrate into the subendothelial space and that remnants activate circulating leukocytes and endothelial cells. Activated monocytes adhere to endothelial adhesion molecules, facilitating subendothelial migration of monocytes. These cells differentiate into macrophages, with the risk of foam cell formation, due to uptake of remnants and modified lipoproteins. Evidence is emerging that specific interventions may reduce the atherogenic postprandial inflammation. Fruits rich in polyphenols, virgin olive oil, carotenoids and exercise have recently been found to reduce postprandial inflammation. Pharmaceutical interventions with fibrates or statins not only improve the overall lipid profile, but reduce postprandial inflammation as well. This review will deal with the current concept of postprandial inflammation in relation to the development of atherosclerosis and potential interventions to reduce postprandial inflammation

La lipidemia posprandial está relacionada con la enfermedad cardiovascular. El concepto patofisiológico actual es que las partículas remanentes traspasan el endotelio, activan los leucocitos y las células endoteliales. Los monocitos activados se adhieren a la paredendotelial por mediación de moléculas de adhesión, facilitando así la migración de los monocitos al espacio subendotelial. Estas células se transforman en macrófagos, convirtiéndose definitivamente en células espumosas después de haber internalizado las partículas remanentes y otras lipoproteínas modificadas. Recientes estudios sugieren que existen intervenciones efectivas para modular la inflamación posprandial, y de esta forma rebajar el riesgo cardiovascular. Frutas ricas en polifenoles, aceite de oliva virgen, el caroteno y el ejercicio son ejemplos que han demostrado una reducción de la inflamación posprandial. El tratamiento con estatinas y fibratos no solo mejora el perfil lipídico, sino que también rebaja la lipidemia posprandial. Esta revisión describe los recientes conceptos de la inflamación posprandial relacionada con la generación de ateroesclerosis y también trata las intervenciones que pueden influir positivamente en la inflamación posprandial

MTP gene polymorphisms and postprandial lipemia in familial combined hyperlipidemia: Effects of treatment with atorvastatin

Background The microsomal triglyceride transfer protein (MTP) is involved in hepatic and intestinal apoB secretion. We studied the effect of the functional MTP-493G/T polymorphism on fasting and postprandial lipoproteins in patients with familial combined hyperlipidemia (FCH) before and after treatment with atorvastatin. Methods Eight FCH heterozygote carriers of the rare -493T allele were compared to 9 matched FCH homozygotes for the wild-type allele in a pilot study. Oral fat loading tests were carried out to measure triglycerides (TG) and apo B48 and B100 in the different fractions of triglyceride-rich lipoproteins (TRLs) before and after treatment with atorvastatin. Results Before treatment, TG were similar between the -493T allele carriers and non-carriers. In the T-allele carriers, a trend was observed for increased postprandial apo B48 and B100 concentrations in Sf > 400 and Sf 60-400 compared to non-carriers. After treatment, fasting and postprandial TG were significantly lowered in carriers of the T allele, but atorvastatin had no effect on postprandial TG in non-carriers. Atorvastatin resulted in similar reductions of apo B48 and B100 in TRLs in both groups. Conclusion The MTP-493G/T polymorphism modulates postprandial apo B48 and apo B100 of TRLs in FCH. Atorvastatin decreases postprandial TG in T-allele carriers with FCH

Antecedentes: La Microsomal Triglyceride Transfer Protein (MTP) participa en la secreción hepática e intestinal de apoB. Hemos estudiado el efecto del polimorfismo funcional MTP-493G/T sobre las lipoproteínas en ayunas o posprandiales en pacientes con hiperlipidemia familiar combinada (FCH) antes y después de un tratamiento con atorvastatina. Métodos: Ocho pacientes FCH heterocigotos para el alelo menos frecuente -493T fueron comparados con 9 pacientes FCH homocigotos para el genotipo salvaje. Tras una sobrecarga oral de grasa se cuantificaron los triglicéridos (TG) y las apoB48 yapoB100 de las diferentes fracciones ricas en TG, antes y después del tratamiento con atorvastatina. Resultados: Antes del tratamiento, los TG eran comparables entre portadores y no portadores del alelo -493T. En portadores del alelo T, se observó una tendencia a mayores concentraciones de apoB48 y apoB100 en las fracciones Sf >400 y Sf 60-400, comparado con los no portadores. Tras el tratamiento, los TG basales y posprandiales fueron significativamente más bajos en portadores del alelo T, pero la atorvastatina no tuvo efecto sobre los TG posprandiales en pacientes no portadores de -493T. La atorvastatina indujo disminuciones en apoB48 y apoB100 de las fracciones ricas en TG tanto en portadores como en no portadores. Conclusión: El polimorfismo -493G/T de la MTP modula el contenido en apoB48 y apoB100 delas lipoproteínas ricas en TG posprandiales. La atorvastatina disminuye los TG posprandiales en pacientes FCH portadores del alelo T

Effect of weight loss on markers of triglyceride-rich lipoprotein metabolism in the metabolic syndrome.

BACKGROUND: Hypertriglyceridaemia, a consistent feature of dyslipidaemia in the metabolic syndrome (MetS), is related to the extent of abdominal fat mass and altered adipocytokine secretion. We determined the effect of weight loss by dietary restriction on markers of triglyceride-rich lipoprotein (TRL) metabolism and plasma adipocytokines. DESIGN: Thirty-five men with MetS participated in a 16 week randomized controlled dietary intervention study. Apolipoprotein (apo) C-III, apoB-48, remnant-like particle (RLP)-cholesterol, total adiponectin, high-molecular weight (HMW) adiponectin, and retinol-binding protein-4 (RBP-4) concentrations were measured using immunoassays. RESULTS: Compared with weight maintenance (n = 15), weight loss (n = 20) significantly decreased body weight, plasma insulin, triglycerides, total cholesterol, low-density lipoprotein (LDL)-cholesterol and lathosterol (P < 0.05). Weight loss also decreased plasma concentrations of apoC-III (-33%), apoB-48 (-37%), very low-density lipoprotein (VLDL)-apoB (-43%), RLP-cholesterol (-48%), and RBP-4 (-20%), and significantly increased plasma total (+20%) and HMW-adiponectin (+19%) concentrations. In the weight loss group, reduction in plasma apoC-III was associated (P < 0.05) with reduction in plasma apoB-48, VLDL-apoB, RLP-cholesterol and triglycerides. Increase in total adiponectin was associated (P < 0.05) with the reduction in plasma VLDL-apoB and triglycerides. The changes in HMW-adiponectin and RBP-4 were not associated with changes in plasma apoB-48, apoC-III, VLDL-apoB, RLP-cholesterol or triglycerides. In multiple regression analysis including changes in visceral fat, insulin and total adiponectin concentrations, the fall in plasma apoC-III concentration was an independent predictor of the reductions in plasma apoB-48, VLDL-apoB, RLP-cholesterol and triglycerides concentrations. CONCLUSIONS: In men with MetS, weight loss decreases the plasma concentrations of apoB-48, VLDL-apoB, RLP-cholesterol and triglycerides. This effect could partly relate to concomitant changes in plasma apoC-III and adiponectin concentrations that accelerate the catabolism of TRLs.