Obesity in db and ob animals leads to impaired hepatic very low density lipoprotein secretion and differential secretion of apolipoprotein B-48 and B-100.
Dyslipidemia secondary to obesity is commonly observed in both animals and humans. As it has been hypothesized that obesity can result in overproduction of VLDL, leading to the subsequent dyslipidemia, we have examined the triglyceride and apoB secretion rates in vivo in obese C57BI/ KsJ db/db and C57BI/6J ob/ob mice and their lean littermates. In ob/ob animals, obesity resulted in significantly lower, not higher, triglyceride secretion rates in both males (3.94 +/- 0.49 mg/h per g liver vs. 5.45 +/- 0.29 mg/h per g liver in lean littermates, P < 0.001) and females (4.29 +/- 0.81 mg/h per g liver vs. 5.25 +/- 0.59 mg/h/g liver, P < 0.001). For db/db, the obese females did not show a statistically significant triglyceride secretion rate compared to their lean littermates. Only the male db/db animals showed a significantly higher triglyceride secretion rate compared with lean littermates (5.50 +/- 1.1 mg/h per g liver vs. 3.37 +/- 0.36 mg/h/g liver, P < 0.001). Examination of the apolipoprotein B (apoB) secretion rates showed that for ob/ob animals and db/db obese females, apoB48 secretion was significantly decreased compared to that of normal littermates, with a small increase in apoB-100 secretion. Total apoB secreted, however, was not increased. Our data further suggest that the predominant cause of the dyslipidemia under these conditions is a defect in removal of VLDL from the circulation.
Li
X
X
Center for Human Nutrition, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas 75235-9052, USA.
Grundy
S M
SM
Patel
S B
SB
D000375:Aging; D000818:Animals; D053299:Apolipoprotein B-100; D053283:Apolipoprotein B-48; D001055:Apolipoproteins B / Q000235:genetics / Q000378:metabolism*; D003920:Diabetes Mellitus / Q000235:genetics / Q000503:physiopathology; D005260:Female; D008079:Lipoproteins, VLDL / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009765:Obesity / Q000235:genetics / Q000503:physiopathology*; D017393:RNA Editing; D012333:RNA, Messenger / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism
D053299:Apolipoprotein B-100; D053283:Apolipoprotein B-48; D001055:Apolipoproteins B; D008079:Lipoproteins, VLDL; D012333:RNA, Messenger; D014280:Triglycerides