Abstract 20466: HyperapoB Women Have Increased Accumulation of ApoC-I on Triglyceride Rich Lipoproteins and Increased Production of ApoC-I by Adipose Tissue
Background: Apolipoprotein C-I (ApoC-I) resides mostly on HDL (90% HDL, 5% VLDL) in the fasted state whereas in the postprandial state there is a transfer of apoC-I to triglyceride-rich lipoproteins (TRL) (80% HDL, >10% TRL). Little is known about the function of apoC-I or its true contribution to dietary fat metabolism and dyslipidemia in human. In vitro assays demonstrate that apoC-I activate LCAT and inhibit CETP, LPL and HL. We have shown that apoC-I is secreted by human adipocytes in culture. The objective of the following study was to examine the role of apoC-I in dietary fat metabolism and increased apoB-lipoprotein number (hyperapoB) in post-menopausal obese women.
Hypothesis: HyperapoB women have increased accumulation of apoC-I on TRL and increased production of apoC-I by adipose tissue.
Methods: 10 post-menopausal obese women with hyperapoB (apoB≥1.2g/L) and 10 controls with normoapoB (<1.2g/L) are being recruited. Fasted and postprandial (66% fat meal) lipoproteins were separated by FPLC. ApoC-I was quantified in 80 FPLC fractions by ELISA. Adipocyte apoC-I secretion was measured in subjects’ adipose tissue biopsy and quantified by ELISA. In situ LPL activity (3H-TG hydrolysis and 3H-NEFA uptake and esterification) of mature 3T3-L1 adipocytes was determined by incubating cells with 3H-TG synthetic lipoproteins (95% TG) and15uM apoC-I.
Results: HyperapoB women had delayed postprandial TRL clearance. HyperapoB women only had 4-fold more fasting apoC-I on HDL vs VLDL compared to normoapoB women who had 18-fold more. This disproportionate distribution was amplified after the fatty meal. Moreover, hyperapoB women had 50% more apoC-I per apoB-lipoprotein particle when compared to controls (p<0.05). Adipose tissue from hyperapoB women secreted more apoC-I over 24h than normoapoB adipose tissue (p<0.05). ApoC-I reduced in situ LPL activity in 3T3-L1 adipocytes in a time-dependent manner up to 49% at 6h (p<0.05).
Conclusion: HyperapoB women have increased apoC-I accumulation on TRL and increased apoC-I production by adipose tissue. We propose that increased adipose tissue apoC-I production and accumulation on TRL decrease adipose tissue TRL clearance, promoting high hepatic TG and NEFA influx and the generation of the hyperapoB phenotype.
- © 2010 by American Heart Association, Inc.