Intestinal absorption of triglyceride and cholesterol. Dietary and pharmacological inhibition to reduce cardiovascular risk.
Triglycerides and cholesterol are important biological lipids, and their excessive intake in the diet is relevant to the development of two prevalent cardiovascular risk factors, obesity and hypercholesterolemia. Because most lipids are essentially water-insoluble molecules, their transport within and absorption from the aqueous medium of intestinal contents is rather complex. This takes place in a series of orderly and interrelated steps, including emulsification, hydrolysis by specific esterases, micellar transport, mucosal absorption, re-synthesis of parent molecules in enterocytes, and assembly with apolipoproteins and other molecules to form chylomicrons, the secretory product of intestinal cells. Many of these processes, however, are not well characterized at the molecular level. While in health the intestinal absorption of triglycerides is very efficient, the same does not apply to cholesterol absorption. Besides being generally inefficient, cholesterol absorption is highly variable, with a between-subject variability that depends in part on genetic factors and an intra-individual variability, which may be modulated by physiological and dietary conditions. All of the sequential steps in intestinal lipid absorption can be interfered with by dietary components or drugs and thus are potential therapeutic targets for inducing a controlled malabsorption of triglyceride, useful in the treatment of obesity, or for rendering cholesterol absorption even more inefficient in an attempt to lower blood cholesterol levels. Nevertheless, intestinally derived cholesterol available to the liver exerts complex feedback regulation on whole-body cholesterol homeostasis that limits the efficacy of cholesterol absorption inhibitors to lower blood cholesterol. This review focuses first on present knowledge of the physiology of intestinal fat absorption, necessary to understand the ways to manipulate it in order to obtain the desired effects on dietary triglyceride and cholesterol disposition. The second part discusses old, present and future ways, both dietary and pharmacological. of interfering with cholesterol and triglyceride absorption to reduce blood cholesterol and energy acquisition, respectively.
Nutrition & Dietetics Service, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clinic i Provincial, Barcelona, Spain. eros@medicina.ub.es
E
E
Ros
D000818:Animals; D002318:Cardiovascular Diseases / Q000517:prevention & control*; D002784:Cholesterol / Q000493:pharmacokinetics*; D004032:Diet; D004041:Dietary Fats / Q000493:pharmacokinetics; D006801:Humans; D006937:Hypercholesterolemia / Q000178:diet therapy / Q000188:drug therapy; D007408:Intestinal Absorption; D009765:Obesity / Q000178:diet therapy / Q000188:drug therapy / Q000378:metabolism; D012307:Risk Factors; D014280:Triglycerides / Q000493:pharmacokinetics*
D004041:Dietary Fats; D014280:Triglycerides; D002784:Cholesterol