Overexpression of lipoprotein lipase improves insulin resistance induced by a high-fat diet in transgenic rabbits
The present study was conducted to determine if direct injections of plasmid pMCKhLPL DNA would lead to sufficient overexpression of lipoprotein lipase (LPL) to reduce plasma triglycerides in mice. After single intramuscular (i.m.) injections, human lipoprotein lipase (hLPL) mRNA was detectable in the quadriceps muscle for at least 21 days. Repeated intraperitoneal (i.p.) and i.m. DNA administration increased the LPL activity in skeletal muscle by 58% (i.p.) and 36% (i.m.) when compared with control-injected mice. A concomitant reduction of plasma triglycerides by 38% (i.p.) and 26% (i.m.) was obtained. Also, repeated measures of plasma triglycerides indicate that the triglyceride-lowering effect of pMCKhLPL can be noted early after DNA injections. Thus, the injection of pMCKhLPL into the peritoneum or quadriceps muscle results in plasma triglyceride reduction in mice.