Changes In Apolipoprotein Composition Research Articles

Changes in apolipoprotein abundance dominate proteome responses to prolonged fasting in elephant seals.

Unlike many animals that reduce activity during fasting, northern elephant seals (NES) undergo prolonged fasting during energy-intensive life-history stages such as reproduction and molting, fueling fasting energy needs by mobilizing fat stores accrued during foraging. NES display several unique metabolic features such as high fasting metabolic rates, elevated blood lipid and high-density lipoprotein (HDL) cholesterol levels, efficient protein sparing and resistance to oxidative stress during fasting. However, the cellular mechanisms that regulate these adaptations are still not fully understood. To examine how metabolic coordination is achieved during prolonged fasting, we profiled changes in blubber, skeletal muscle and plasma proteomes of adult female NES over a 5week fast associated with molting. We found that while blubber and muscle proteomes were remarkably stable over fasting, over 50 proteins changed in abundance in plasma, including those associated with lipid storage, mobilization, oxidation and transport. Apolipoproteins dominated the blubber, plasma and muscle proteome responses to fasting. APOA4, APOE and APOC3, which are associated with lipogenesis and triglyceride accumulation, decreased, while APOA1, APOA2 and APOM, which are associated with lipid mobilization and HDL function, increased over fasting. Our findings suggest that changes in apolipoprotein composition may underlie the maintenance of high HDL levels and, together with adipokines and hepatokines that facilitate lipid catabolism, may mediate the metabolic transitions between feeding and fasting in NES. Many of these proteins have not been previously studied in this species and provide intriguing hypotheses about metabolic regulation during prolonged fasting in mammals.

The interaction of lipolysis products of very low density lipoprotein with plasma high density lipoprotein (HDL): perfusate HDL with plasma HDL subfractions.

The nature of the interaction of high density lipoproteins (HDL), formed during lipolysis of human very low density lipoprotein (VLDL) by perfused rat heart, with subfractions of human plasma HDL was investigated. Perfusate HDL, containing apoliproproteins (apo) E, C-II, and C-III but no apo A-I or A-II, was incubated with a subfraction of HDL (HDL-A) containing apo A-I and A-II, but devoid of apo C-II, C-III, and E. The products of the incubation were resolved by heparin-Sepharose or hydroxylapatite chromatography under conditions which allowed the resolution of the initial HDL-A and perfusate HDL. The fractions were analyzed for apolipoprotein content and lipid composition and assessed for particle size by electron microscopy. Following the incubation, the apo-E-containing lipoproteins were distinct from perfusate HDL since they contained apo A-I as a major component and apo C-II and C-III in reduced proportions. However, the HDL-A fraction contained apo C-II and C-III as major constituents. Associated with these changes in apolipoprotein composition, the apo-E-rich lipoproteins acquired cholesteryl ester from the HDL-A fraction and lost phospholipid to the HDL-A fraction. The HDL-A fraction maintained a low unesterified cholesterol/phospholipid molar ratio (0.23), while the apo-E-containing lipoproteins possessed a high ratio (0.75) characteristic of the perfusate HDL.(ABSTRACT TRUNCATED AT 250 WORDS)

Changes in lipid and apolipoprotein composition of pig lipoproteins facilitated by rabbit lipid transfer protein

A lipid transfer protein has been purified from the lipoprotein-free fraction of rabbit plasma. Rabbit lipid transfer protein, which was purified 600–700-fold with a 4% recovery, has an apparent M r. of 68000 and facilitates the transfer of isotopically labelled cholesterol ester, triacylglycerol and phosphatidylcholine between low-density lipoprotein (LDL) and high-density lipoprotein (HDL). Rabbit lipid transfer protein, which appears to be very similar to the cholesteryl ester exchange protein previously purified from human plasma, was incubated with pig plasma at 37° C for up to 6 h. Analysis of very-low-density lipoprotein (VLDL, d < 1.006 g/ml), LDL ( d 1.019−1.063 g/ml) and HDL ( d 1.090−1.21 g/ml) after incubation showed that lipid transfer protein had a marked effect on the composition of the lipoprotein classes. The VLDL became enriched with cholesteryl ester and depleted of triacylglycerol. The LDL and HDL became enriched with triacylglycerol. In addition to these changes in lipid composition there were also changes in apolipoprotein composition. The most prominent change in apolipoprotein distribution was a marked increase in the apolipoprotein E content of LDL which was observed only after incubation in the presence of lipid transfer protein.