Apolipoprotein A-V deficiency results in marked hypertriglyceridemia attributable to decreased lipolysis of triglyceride-rich lipoproteins and removal of their remnants

Itamar Grosskopf, Nadine Baroukh, Sung Joon Lee, Yehuda Kamari, Dror Harats, Edward M. Rubin, Len A. Pennacchio, Allen D. Cooper

Research output: Contribution to journalArticle

107 Citations (Scopus)

Abstract

Objective - ApoAV, a newly discovered apoprotein, affects plasma triglyceride level. To determine how this occurs, we studied triglyceride-rich lipoprotein (TRL) metabolism in mice deficient in apoAV. Methods and Results - No significant difference in triglyceride production rate was found between apoa5-/- mice and controls. The presence or absence of apoAV affected TRL catabolism. After the injection of 14C-palmitate and 3H-cholesterol labeled chylomicrons and 125I-labeled chylomicron remnants, the disappearance of 14C, 3H, and 125I was significantly slower in apoa5-/- mice relative to controls. This was because of diminished lipolysis of TRL and the reduced rate of uptake of their remnants in apoa5-/- mice. Observed elevated cholesterol level was caused by increased high-density lipoprotein (HDL) cholesterol in apoa5-/- mice. VLDL from apoa5-/- mice were poor substrate for lipoprotein lipase, and did not bind to the low-density lipoprotein (LDL) receptor as well as normal very-low-density lipoprotein (VLDL). LDL receptor levels were slightly elevated in apoa5-/- mice consistent with lower remnant uptake rates. These alterations may be the result of the lower apoE-to-apoC ratio found in VLDL isolated from apoa5-/- mice. Conclusions - These results support the hypothesis that the absence of apoAV slows lipolysis of TRL and the removal of their remnants by regulating their apoproteins content after secretion.

Original languageEnglish
Pages (from-to)2573-2579
Number of pages7
JournalArteriosclerosis, thrombosis, and vascular biology
Volume25
Issue number12
DOIs
Publication statusPublished - 2005 Dec

Keywords

  • Apoa5
  • Hypertriglyceridemia
  • Knockout
  • Lipolysis
  • Triglyceride-rich lipoproteins

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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