Enhanced expression of hepatic acyl-coenzyme A synthetase and microsomal triglyceride transfer protein messenger RNAs in the obese and hypertriglyceridemic rat with visceral fat accumulation

被引:73
作者
Kuriyama, H
Yamashita, S
Shimomura, I
Funahashi, T
Ishigami, M
Aragane, K
Miyaoka, K
Nakamura, T
Takemura, K
Man, ZW
Toide, K
Nakayama, N
Fukuda, Y
Lin, MCL
Wetterau, JR
Matsuzawa, Y
机构
[1] Osaka Univ, Sch Med, Dept Internal Med 2, Osaka 565, Japan
[2] Otsuka Pharmaceut Co Ltd, Tokushima Res Inst, Tokushima 77101, Japan
[3] Otsuka Pharmaceut Co Ltd, Otsuka Assay Labs, Tokushima, Japan
[4] Bristol Myers Squibb Co, Dept Metab Dis, Princeton, NJ USA
关键词
D O I
10.1002/hep.510270233
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
The liver plays a central role in lipoprotein metabolism. In particular, very-low density lipoprotein (VLDL) is assembled in the hepatocytes and secreted into the blood circulation. The VLDL is then catabolized to low-density lipoprotein by lipoprotein lipase and hepatic triglyceride lipase. Obese subjects, especially those with visceral fat accumulation, are frequently associated with hyperlipidemia, non-insulin-dependent diabetes mellitus (NIDDM), and hypertension. The mechanism of hyperlipidemia in visceral fat obesity has not yet been elucidated. Otsuka Long-Evans Tokushima Fatty (OLETF) rat is an animal model of NIDDM, characterized by obesity with visceral fat accumulation, hyperlipidemia, and late-onset insulin resistance. To elucidate the mechanism of hyperlipidemia observed in OLETF rats, we focused on the production of VLDL by the liver and investigated hepatic messenger RNA (mRNA) levels of microsomal triglyceride transfer protein (MTP), acyl-coenzyme A synthetase (ACS), and apolipoprotein B (apo B), which play important roles in VLDL synthesis and secretion. In 6-week-old OLETF rats, in which insulin resistance had not been manifested, visceral fat weight was already higher and portal free fatty acid (FFA) and VLDL-triglyceride levels were elevated compared with the control rats. Hepatic ACS activity and mRNA levels, and MTP mRNA levels were also increased in OLETF rats, whereas apo B mRNA levels were similar; these results suggest that the enhanced expression of both ACS and MTP genes associated with visceral fat accumulation before developing insulin resistance may be involved in the pathogenesis of hyperlipidemia in obese animal models with NIDDM.
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页码:557 / 562
页数:6
相关论文
共 45 条
[41]   N-3 FATTY-ACIDS STIMULATE INTRACELLULAR DEGRADATION OF APOPROTEIN-B IN RAT HEPATOCYTES [J].
WANG, HX ;
CHEN, XL ;
FISHER, EA .
JOURNAL OF CLINICAL INVESTIGATION, 1993, 91 (04) :1380-1389
[42]  
WEINER FR, 1991, J BIOL CHEM, V266, P23525
[43]  
WETTERAU JR, 1992, SCIENCE, V258, P999
[44]  
WETTERAU JR, 1990, J BIOL CHEM, V265, P9800
[45]   PURIFICATION AND CHARACTERIZATION OF MICROSOMAL TRIGLYCERIDE AND CHOLESTERYL ESTER TRANSFER PROTEIN FROM BOVINE LIVER-MICROSOMES [J].
WETTERAU, JR ;
ZILVERSMIT, DB .
CHEMISTRY AND PHYSICS OF LIPIDS, 1985, 38 (1-2) :205-222