Diurnal Regulation of Microsomal Triglyceride Transfer Protein and Plasma Lipid Levels

Abstract

Plasma lipids are maintained within a narrow physiologic range and exhibit circadian rhythmicity. Plasma triglyceride and cholesterol levels were high in the night due to changes in apolipoprotein B-lipoproteins in ad libitum fed rats and mice maintained in a 12-h photoperiod. Absorption of [(3)H]triolein or [(3)H]cholesterol was higher at 2400 h than at 1200 h, indicating that intestinal lipoprotein production shows diurnal variation. Moreover, intestinal microsomal triglyceride transfer protein (MTP) activity, protein, mRNA, and gene transcription showed diurnal variations and were high at 2400 h. Similar to the small intestine, hepatic MTP activity, protein, and mRNA levels also changed significantly within a day. MTP was induced in fasted animals soon after refeeding. When mice were subjected to restricted feeding, MTP expression was high at the expected time of food availability. In contrast, extended exposures to light and dark completely abolished rhythmicity in MTP expression and plasma lipid levels. These studies show that MTP expression and plasma lipid undergo diurnal regulation and exhibit peaks and nadirs at similar times and suggest that diurnal modulation of MTP is a major determinant of daily changes in plasma lipids. Furthermore, environmental factors, such as food and light, play an important role in MTP regulation.