Central LIF gene therapy suppresses food intake, body weight, serum leptin and insulin for extended periods.
Leukemia inhibitory factor (LIF) overexpression, induced by the intracerebroventricular (i.c.v.) injection of an recombinant adeno-associated viral vector encoding LIF (rAAV-LIF), resulted in a dose-dependent reduction in body weight (BW) gain, food intake (FI) and adiposity, evidenced by suppression of serum leptin and free fatty acids for an extended period in outbred adult female rats. A dose-dependent reduction in serum insulin levels and unchanged serum glucose, energy expenditure through thermogenesis as indicated by uncoupling protein-1 (UCP-1) mRNA expression in brown adipose tissue (BAT), and metabolism as indicated by serum T3 and T4, accompanied the blockade of weight gain. Thus, central rAAV-LIF therapy is a viable strategy to voluntarily reduce appetite and circumvent leptin resistance, a primary factor underlying age-dependent weight gain and obesity in rodents and humans.
Beretta
Elena
E
Department of Neuroscience, College of Medicine, University of Florida McKnight Brain Institute, Gainesville, FL 32610-0244, USA.
Dhillon
Harveen
H
Kalra
Pushpa S
PS
Kalra
Satya P
SP
D002001:Adipose Tissue, Brown / Q000378:metabolism; D000818:Animals; D001066:Appetite / Q000235:genetics*; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight / Q000235:genetics*; D001921:Brain / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D005260:Female; D015316:Genetic Therapy; D006131:Growth Inhibitors / Q000032:analysis / Q000235:genetics* / Q000502:physiology*; D007328:Insulin / Q000097:blood*; D015850:Interleukin-6; D007473:Ion Channels; D020738:Leptin / Q000097:blood*; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000032:analysis / Q000235:genetics* / Q000502:physiology*; D008565:Membrane Proteins / Q000235:genetics; D024101:Mitochondrial Proteins; D009765:Obesity / Q000097:blood / Q000235:genetics / Q000628:therapy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D000071256:Uncoupling Protein 1
D001786:Blood Glucose; D002352:Carrier Proteins; D006131:Growth Inhibitors; D007328:Insulin; D015850:Interleukin-6; D007473:Ion Channels; D020738:Leptin; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; C000604371:UCP1 protein, human; C000604373:Ucp1 protein, rat; D000071256:Uncoupling Protein 1