Apoprotein C-III deficiency markedly stimulates triglyceride secretion in vivo: comparison with apoprotein E.
Apoprotein (apo) C-III plays an important role in the development of hypertriglyceridemia by inhibiting triglyceride (TG) removal. However, the effect of apo C-III on TG production remains unclear. We measured TG secretion rate (TGSR) in apo C-III gene-disrupted (apo C-III-null) mice to investigate the influence of this protein on TG turnover. TGSR measured by the Triton WR-1339 method was increased twofold in these mice compared with wild-type (WT) mice. Obesity was induced by the injection of gold-thioglucose (GTG), which made the WT mice hypertriglyceridemic due to a threefold increase of TGSR. However, GTG-induced obesity failed to increase TG in apo C-III-null mice, although TGSR was increased 10-fold, suggesting substantial stimulation of TG removal. Apo E-null mice were severely hypercholesterolemic but were not hypertriglyceridemic, and TGSR was rather decreased. GTG-induced obesity made these mice hypertriglyceridemic because of TG overproduction to an extent similar to that seen in WT mice. These results suggest that apo C-III deficiency potently enhances TG turnover, especially when TG production is stimulated, and that apo E deficiency is not always rate limiting for TG production.
Hirano
T
T
First Department of Internal Medicine, Showa University School of Medicine, Tokyo 142-8666, Japan.
Takahashi
T
T
Saito
S
S
Tajima
H
H
Ebara
T
T
Adachi
M
M
D000818:Animals; D053305:Apolipoprotein C-III; D001056:Apolipoproteins C / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D006051:Aurothioglucose / Q000031:analogs & derivatives; D001786:Blood Glucose / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D003902:Detergents; D006720:Homozygote; D015228:Hypertriglyceridemia / Q000235:genetics / Q000378:metabolism*; D007328:Insulin / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000139:chemically induced / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000494:pharmacology; D014280:Triglycerides / Q000097:blood / Q000378:metabolism*
D053305:Apolipoprotein C-III; D001056:Apolipoproteins C; D001057:Apolipoproteins E; D001786:Blood Glucose; D003902:Detergents; D007328:Insulin; D014280:Triglycerides; C032871:gold thiogluconate; D006051:Aurothioglucose; D011092:Polyethylene Glycols; D002784:Cholesterol; C016811:tyloxapol