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 hypert riglyceridemia by inhibiting triglyceride (TG) removal. However, the effect of apo C-III on TG production remains unclear. We measured TG secretion ra te (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 W R-1339 method was increased twofold in these mice compared with wild-type ( WT) mice. Obesity was induced by the injection of gold-thioglucose (GTG), w hich made the WT mice hypertriglyceridemic due to a threefold increase of T GSR. However, GTG-induced obesity failed to increase TG in apo C-III-null m ice, 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 obesi ty made these mice hypertriglyceridemic because of TG overproduction to an extent similar to that seen in WT mice. These results suggest that apo C-II I deficiency potently enhances TG turnover, especially when TG production i s stimulated, and that apo E deficiency is not always rate limiting for TG production.