Apolipoprotein CIII deficiency prevents the development of hypertriglyceridemia in streptozotocin-induced diabetic mice.
To explore the role of apolipoprotein (apo) CIII in the development of hypertriglyceridemia associated with diabetes mellitus, we examined triglyceride (TG) kinetics in apo CIII - deficient mice (apo CIII - null) and wild-type (WT) (C57BL/6J) mice with diabetes induced by the injection of streptozotocin (STZ). Plasma TG levels increased significantly in WT mice after diabetes was induced (102 +/- 29 v 65 +/- 33 mg/dL, P <.01). Apo CIII-null mice had a significantly lower TG level (35 +/- 9 mg/dL) that remained unchanged even when diabetes was induced (35 +/- 8 mg/dL). The TG secretion rate (TGSR) measured by the Triton WR1339 method tended to decrease in diabetic WT, indicating that catabolism of TG was impaired. Apo CIII-null mice showed 2-fold higher TG production than WT mice, indicating markedly faster clearance of TG. The high TGSR was halved when diabetes was induced in apo CIII-null mice, and the fractional catabolic rate (FCR) of TG was also halved, although it was still significantly higher than in WT mice. Lipoprotein lipase (LPL) activity in postheparin plasma was not significantly altered in WT or apo CIII-null mice regardless of the presence or absence of diabetes. [(3)H] very-low-density lipoprotein (VLDL)-TG from WT or apo CIII-null mice showed similar clearance by WT recipients, and this was also observed when VLDL was obtained from diabetic counterparts. In contrast, VLDL-TG was cleared faster by apo CIII-null recipients compared with WT recipients, regardless of the VLDL donors. These results suggest that apo CIII deficiency prevents the development of hypertriglyceridemia associated with diabetes by stimulating TG removal, possibly by promoting the interaction of VLDL with the TG removal system.
Takahashi
Toshihiro
T
Department of Internal Medicine, Showa University School of Medicine, Tokyo, Japan.
Hirano
Tsutomu
T
Okada
Kenta
K
Adachi
Mitsuru
M
D000818:Animals; D053305:Apolipoprotein C-III; D001056:Apolipoproteins C / Q000172:deficiency*; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D002784:Cholesterol / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000097:blood*; D015228:Hypertriglyceridemia / Q000097:blood / Q000517:prevention & control*; D008079:Lipoproteins, VLDL / Q000097:blood; D008297:Male; D051379:Mice; D013997:Time Factors; D014280:Triglycerides / Q000097:blood
D053305:Apolipoprotein C-III; D001056:Apolipoproteins C; D001786:Blood Glucose; D008079:Lipoproteins, VLDL; D014280:Triglycerides; D002784:Cholesterol