Hepatic VLDL assembly is disturbed in a rat model of nonalcoholic fatty liver disease: is there a role for dietary coenzyme Q?
The overproduction of very-low-density lipoprotein (VLDL) is a characteristic feature of nonalcoholic fatty liver disease (NAFLD). The aim of this study was to use a high-fat diet-induced model of NAFLD in rats to investigate 1) the influence of the disease on hepatic VLDL processing in the endoplasmic reticulum and 2) the potential modulatory effects of dietary coenzyme Q (CoQ). Rats were fed a standard low-fat diet (control) or a diet containing 35% fat (57% metabolizable energy). After 10 wk, high-fat diet-fed animals were divided into three groups: the first group was given CoQ9 (30 mg*kg body wt(-1)*day(-1) in 0.3 ml olive oil), the second group was given olive oil (0.3 ml/day) only, and the third group received no supplements. Feeding (3 high-fat diets and the control diet) was then continued for 8 wk. In all high-fat diet-fed groups, the content of triacylglycerol (TG) and cholesterol in plasma VLDL, the liver, and liver microsomes was increased, hepatic levels of apolipoprotein B48 were raised, and the activities of microsomal TG transfer protein and acyl CoA:cholesterol acyltransferase were reduced. These findings provide new evidence indicating that VLDL assembly and the inherent TG transfer to the endoplasmic reticulum are altered in NAFLD and suggest a possible explanation for both the overproduction of VLDL associated with the condition and the disease etiology itself. Dietary CoQ caused significant increases in apolipoprotein B mRNA and microsomal TG levels and altered the phospholipid content of microsomal membranes. These changes, however, may not be beneficial as they may lead to the secretion of larger, more atherogenic VLDL.
Cano
Ainara
A
Department of Veterinary Basic Sciences, Royal Veterinary College, London NW1 0TU, United Kingdom.
Ciaffoni
Fiorella
F
Safwat
Ghada M
GM
Aspichueta
Patricia
P
Ochoa
Begoña
B
Bravo
Elena
E
Botham
Kathleen M
KM
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001055:Apolipoproteins B / Q000378:metabolism; D004032:Diet; D005234:Fatty Liver / Q000378:metabolism*; D050356:Lipid Metabolism / Q000502:physiology; D008079:Lipoproteins, VLDL / Q000097:blood / Q000302:isolation & purification / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014451:Ubiquinone / Q000031:analogs & derivatives / Q000378:metabolism*
D000975:Antioxidants; D001055:Apolipoproteins B; D008079:Lipoproteins, VLDL; D012333:RNA, Messenger; D014451:Ubiquinone; C024989:coenzyme Q10; C030571:ubiquinone 9