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

The liver plays a central role in lipoprotein metabolism. In particula r, 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 triglyce ride lipase. Obese subjects, especially those with visceral fat accumu lation, are frequently associated with hyperlipidemia, non-insulin-dep endent diabetes mellitus (NIDDM), and hypertension. The mechanism of h yperlipidemia in visceral fat obesity has not yet been elucidated. Ots uka Long-Evans Tokushima Fatty (OLETF) rat is an animal model of NIDDM , characterized by obesity with visceral fat accumulation, hyperlipide mia, 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) level s of microsomal triglyceride transfer protein (MTP), acyl-coenzyme A s ynthetase (ACS), and apolipoprotein B (apo B), which play important ro les in VLDL synthesis and secretion. In 6-week-old OLETF rats, in whic h 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 activ ity and mRNA levels, and MTP mRNA levels were also increased in OLETF rats, whereas apo B mRNA levels were similar; these results suggest th at the enhanced expression of both ACS and MTP genes associated with v isceral fat accumulation before developing insulin resistance may be i nvolved in the pathogenesis of hyperlipidemia in obese animal models w ith NIDDM.