Intestinally derived lipids: metabolic regulation and consequences--an overview

Area of Science:

• Metabolic research
• Nutritional science
• Molecular biology

Background:

• Dietary factors significantly influence postprandial metabolism, but precise mechanisms remain unclear.
• The regulation of postprandial lipemia involves numerous molecular players acting as gatekeepers.
• The need for a standardized oral lipid tolerance test is questioned due to variability in meal components.

Purpose of the Study:

• To review the roles of specific proteins and hormones in regulating postprandial lipemia.
• To identify key gatekeepers within the intestine, periphery, and liver.
• To explore potential targets for therapeutic regulation of lipid metabolism.

Main Methods:

• Review of literature on transporters, enzymes, receptors, and hormones involved in lipid metabolism.
• Discussion of findings from studies using knockout mouse models (C3 KO, C5L2 KO).
• Analysis of the roles of specific proteins like FABP2, MTP, NPC1-L1, LPL, SR-B1, and ABCA1.

Main Results:

• Intestinal gatekeepers (FABP2, MTP, NPC1-L1) are essential for chylomicron formation and cholesterol absorption.
• Peripheral gatekeepers (LPL, ASP, insulin, TNFalpha) control fatty acid clearance and tissue uptake.
• Deficiency in ASP or C5L2 in mice led to increased postprandial lipemia, compensated by enhanced energy expenditure and muscle lipid oxidation.
• Hepatic clearance is regulated by factors including SR-B1 and ABCA1.

Conclusions:

• Intestinal, peripheral, and hepatic gatekeepers play distinct and vital roles in managing postprandial lipemia.
• These gatekeepers represent potential targets for modulating lipid metabolism and addressing metabolic disorders.
• Further research into these mechanisms could inform the development of standardized lipid tolerance tests.