Mice body weight gain is prevented after naked human leptin cDNA transfer into skeletal muscle by electroporation.
BACKGROUND
In this investigation, the feasibility of gene therapy for obesity by electroporational transfer of naked plasmid with leptin cDNA into skeletal muscle was tested. Both young and adult mice were studied.


METHODS
Human leptin cDNA was attached to the human insulin precursor secretion signal peptide gene. The fused gene was then inserted into the mammalian expression vector pcDNA3.1(-) and transferred into skeletal muscle of normal female mice using electroporation.


RESULTS
During the time of exogenic gene expression, daily food intake of leptin cDNA-treated mice was observed to be lower than the control. The body weight gain was prevented efficaciously regardless of if they were young or adult. At the 7th week after gene transfer, the body weight of both young and adult leptin cDNA-treated mice was about 20% lighter than the control. Although the body weight of pair fed controlled adult mice was close to the leptin cDNA-treated mice at the 8th week, they were always heavier than the leptin cDNA-treated mice before this time. The levels of retroperitoneal fats and serum TG of leptin cDNA-treated mice were markedly lower than that of the control. The relative serum hyperleptinemic level could last for about 2 months. The expression of leptin cDNA in muscle cells was also detected by RT-PCR. The levels of serum insulin and glucose of leptin cDNA-treated mice decreased slightly. Our data also showed that the hyperleptinmia resulted in uterus expansion in young mice, but not in the adults.


CONCLUSIONS
The present study provides evidence of successful electroporation of naked plasmid DNA transfer for prevention or treatment of mice obesity.
Wang
Xue-Dong
XD
National Laboratory of Protein Engineering and Plant Genetic Engineering, College of Life Sciences, Peking University, Beijing 100871, PR China.
Liu
Jian
J
Yang
Ji-Chun
JC
Chen
Wei-Qiang
WQ
Tang
Jian-Guo
JG
D000273:Adipose Tissue; D000818:Animals; D001786:Blood Glucose; D001831:Body Temperature; D018076:DNA, Complementary / Q000235:genetics* / Q000378:metabolism / Q000627:therapeutic use; D004195:Disease Models, Animal; D004435:Eating; D018274:Electroporation; D005260:Female; D015870:Gene Expression; D015316:Genetic Therapy; D006801:Humans; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood / Q000235:genetics / Q000627:therapeutic use*; D051379:Mice; D018482:Muscle, Skeletal / Q000378:metabolism*; D009765:Obesity / Q000188:drug therapy* / Q000235:genetics; D010957:Plasmids / Q000235:genetics; D011863:Radioimmunoassay; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014280:Triglycerides / Q000097:blood; D015431:Weight Loss / Q000235:genetics
D001786:Blood Glucose; D018076:DNA, Complementary; D007328:Insulin; D020738:Leptin; D014280:Triglycerides