Basal, endogenous leptin is metabolically active in newborn rat pups.
OBJECTIVE
The adipocyte-derived hormone leptin regulates food intake and body weight via the activation of JAK-STAT pathway in mammalian adult hypothalamic neurons. To investigate whether endogenous leptin is metabolically active in newborn rat pups, the JAK-STAT leptin signaling pathway was analyzed following leptin antagonist challenge.


METHODS
One day old male control pups were injected with either (i) saline, (ii) leptin (10 μg/g, s.c; n=4), (iii) pegylated leptin antagonist (PEG-MLA, 20 μg/g, s.c, n=4), or (iv) leptin plus PEG-MLA. Hypothalamus was dissected from individual pups at 30, 45, and 60 min. Protein expression of ObR, STAT3, pSTAT3, and SOCS3 was analyzed by Western blot.


RESULTS
Leptin, but not PEG-MLA, produced a significant increase in hypothalamic pSTAT3 relative to saline treatment. Systemically administered PEG-MLA effectively blocks leptin signal induction of hypothalamic JAK-STAT signaling. The presence of PEG-MLA in combination with leptin attenuated the leptin-induced increase in pSTAT3.


CONCLUSIONS
Thus, basal leptin levels are metabolically active in the newborn rats. These results brings new insights in considering the importance of endogenous leptin at birth, especially in low birth weight offspring who may be predisposed to altered neurogenesis and later obesity, and provide potential therapeutic strategies for programmed or diet-induced obesity.
UPSP-EGEAL Institut Polytechnique LaSalle de Beauvais, 19 Rue Pierre Waguet, Beauvais Cedex, France. latifa.najar@lasalle-beauvais.fr
Latifa
L
Abdennebi-Najar
Mina
M
Desai
Guang
G
Han
Ederlen
E
Casillas
Djiane
D
Jean
Gertler
G
Arieh
Michael G
MG
Ross
D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D001481:Basal Metabolism / Q000187:drug effects / Q000502:physiology*; D005260:Female; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D020738:Leptin / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D011092:Polyethylene Glycols / Q000494:pharmacology; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D054411:Receptors, Leptin / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013997:Time Factors
D020738:Leptin; D054411:Receptors, Leptin; D050796:STAT3 Transcription Factor; C484843:pegylated leptin; D011092:Polyethylene Glycols