Mutated-leptin gene transfer induces increases in body weight by electroporation and hydrodynamics-based gene delivery in mice.
To investigate whether in vivo gene transfer causes leptin-antagonistic effects on food intake, animal body weight and fat tissue weight, the R128Q mutated-leptin gene, an R to Q substitution at position 128 of mouse leptin, was transferred into mouse liver and leg muscle by electroporation and hydrodynamics-based gene delivery. Mutated-leptin gene transfer by electroporation caused significant increases in body weight at 5 days and after (5.4% increase relative to control; p<0.05). Hydrodynamics-based gene delivery of the mutated-leptin gene also caused an increase in body weight (3.0% increase relative to control; p<0.05). Mutated-leptin gene transfer by electroporation significantly increased the tissue weight of epididymal white fat and neuropeptide Y mRNA expression in the hypothalamus compared with those of the control group 3 weeks after gene transfer (p<0.05). These results suggest that mutated-leptin gene transfer successfully produced leptin-antagonistic effects by modulating the central regulator of energy homeostasis. Also, the extent of leptin-antagonistic effects by electroporation was much higher than hydrodynamics-based gene delivery, with at least single gene transfer.
Xiang
Lan
L
Laboratory of Animal Nutrition, Department of Applied Molecular Biosciences, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan.
Murai
Atsushi
A
Muramatsu
Tatsuo
T
D002001:Adipose Tissue, Brown; D054369:Agouti-Related Protein; D000818:Animals; D001835:Body Weight / Q000235:genetics*; D002352:Carrier Proteins / Q000378:metabolism; D004435:Eating; D018274:Electroporation / Q000379:methods*; D004734:Energy Metabolism; D018014:Gene Transfer Techniques; D007031:Hypothalamus; D036341:Intercellular Signaling Peptides and Proteins; D007473:Ion Channels; D020738:Leptin / Q000097:blood / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D024101:Mitochondrial Proteins; D009154:Mutation / Q000235:genetics*; D009478:Neuropeptide Y / Q000378:metabolism; D017354:Point Mutation; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017422:Sequence Analysis, DNA; D000071256:Uncoupling Protein 1
D054369:Agouti-Related Protein; D002352:Carrier Proteins; D036341:Intercellular Signaling Peptides and Proteins; D007473:Ion Channels; D020738:Leptin; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D009478:Neuropeptide Y; D011506:Proteins; D012333:RNA, Messenger; D000071256:Uncoupling Protein 1