Hypertriglyceridemia in Watanabe heritable hyperlipidemic rabbits was associated with increased production and reduced catabolism of very-low-density lipoproteins.
Watanabe heritable hyperlipidemic (WHHL) rabbit is an animal model for human familial hypercholesterolemia. Recently, we segregated a new mutant of WHHL rabbits with plasma levels of triglycerides (TG) >500 mg/dl (designated as TGH-WHHL). To investigate the underlying mechanisms for hypertriglyceridemia, we compared TGH-WHHL with WHHL rabbits with lower plasma TG levels (<250 mg/dl, designated as TGL-WHHL). A Triton WR-1339 injection experiment revealed that TGH-WHHL rabbits had increased secretion and decreased clearance of TG-rich lipoproteins. Furthermore, TGH-WHHL rabbits had lower a post-heparin activity of lipoprotein lipase and a higher cholesterol ester transfer protein activity than TGL-WHHL rabbits. Cultured hepatocytes isolated from TGH-WHHL rabbits showed a higher secretion rate of TG and cholesterol than those of TGL-WHHL rabbits. In addition, TGH-WHHL rabbits exhibited marked insulin resistance. These data suggest that hypertriglyceridemia exhibited by WHHL rabbits is caused by both increased production and impaired catabolism of TG-rich lipoproteins and associated with insulin resistance.
Zhang
Chuan
C
Department of Metabolism and Endocrinology, Zhong Shan Affiliated Hospital, Dalian University, Dalian 116001, China. zhangb3jp2002@yahoo.co.jp
Jin
Yingji
Y
Liu
Tiequn
T
Liu
Feng
F
Ito
Tsunekata
T
D000818:Animals; D030801:Animals, Genetically Modified; D002478:Cells, Cultured; D053480:Cholesterol Ester Transfer Proteins / Q000378:metabolism; D015243:Cholesterol, VLDL / Q000378:metabolism*; D004195:Disease Models, Animal; D005951:Glucose Tolerance Test; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D015228:Hypertriglyceridemia / Q000188:drug therapy / Q000378:metabolism*; D007150:Immunohistochemistry; D007178:Inbreeding; D007328:Insulin / Q000032:analysis; D008071:Lipoprotein Lipase / Q000378:metabolism; D008297:Male; D010179:Pancreas / Q000737:chemistry / Q000473:pathology; D011092:Polyethylene Glycols / Q000494:pharmacology; D011817:Rabbits; D013045:Species Specificity; D013501:Surface-Active Agents / Q000494:pharmacology; D014280:Triglycerides / Q000097:blood / Q000378:metabolism
D053480:Cholesterol Ester Transfer Proteins; D015243:Cholesterol, VLDL; D007328:Insulin; D013501:Surface-Active Agents; D014280:Triglycerides; D011092:Polyethylene Glycols; D008071:Lipoprotein Lipase; C016811:tyloxapol