Long-term control of food intake and body weight by hydrodynamics-based delivery of plasmid DNA encoding leptin or CNTF.
BACKGROUND
Obesity contributes to many common diseases, including cardiovascular and metabolic disorders such as diabetes, hypertension, and stroke. Leptin and ciliary neurotrophic factor (CNTF), two members of the cytokine family, play important roles in controlling food intake and body weight in rodents. Here, we used the hydrodynamics-based gene delivery technique to introduce leptin and CNTF expression plasmids, pCAGGS-leptin and pCAGGS-CNTF, into mice and to assess whether they could induce high expression of leptin or CNTF and reduce food intake and body weight in the mice.


METHODS
Plasmid DNA (50 microg) in lactated Ringer's solution (0.1 ml/g body weight) was rapidly injected into the tail vein of 4-week-old male MCH-ICR mice.


RESULTS
After a single injection, serum leptin peaked (at 32.0 +/- 3.1 ng/ml) 2 days after the injection, and serum CNTF peaked (at 22.0 +/- 0.8 microg/ml) 1 day after the injection. The high expression of either leptin or CNTF was sustained and dramatically reduced food intake (CNTF and leptin group vs. control group; 2.3 +/- 0.5 and 3.1 +/- 0.5 g/day vs. 4.8 +/- 0.6 g/day; p < 0.001) and body weight (3 weeks after the injection; CNTF and leptin group vs. control group; -19.5% and +3.3% vs. +33.3-47.5%; p < 0.001) in the mice, suggesting potent in vivo activities for these exogenously expressed proteins.


CONCLUSIONS
These results suggest that hydrodynamics-based gene delivery could have broad applications in the study of appetite regulation and metabolism.
Division of Stem Cell Regulation Research (G6), Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Jingjing
J
Jiang
Eiji
E
Yamato
Jun-ichi
J
Miyazaki
D000818:Animals; D015153:Blotting, Western; D001835:Body Weight / Q000235:genetics; D020934:Ciliary Neurotrophic Factor / Q000097:blood / Q000235:genetics / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004435:Eating / Q000235:genetics; D015870:Gene Expression; D015316:Genetic Therapy; D007124:Immunoenzyme Techniques; D020738:Leptin / Q000097:blood / Q000235:genetics / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009765:Obesity / Q000188:drug therapy* / Q000235:genetics; D010957:Plasmids / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D020934:Ciliary Neurotrophic Factor; D020738:Leptin