Basal, endogenous leptin is metabolically active in newborn rat pups

Abstract

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.

Keywords:

• Leptin antagonist (PEG-MLA)
• JAK-STAT signaling pathway
• hypothalamus
• neurogenesis
• low birth weight
• obesity
• developmental programming

Acknowledgements

This work was supported by SMFM-AAOGF fellowship award to RZM. The authors thank Qinghai Liu, Linda Day, Stacy Behare, and Karina Cervantez for their technical assistance and Valérie Leroux, Véronique Llorens, and Philippe Choquet for their constant support.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.