Effects of subcutaneous leptin injections on hypothalamic gene profiles in lean and ob/ob mice

Jiuhua Duan, Yang Ho Choi, Diane Hartzell, Mary Anne Della-Fera, Mark Hamrick, Clifton A. Baile

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Abstract

Objective: Leptin-deficient ob/ob mice are more sensitive to exogenous leptin than lean mice and leptin treatment normalizes many of the phenotypic characteristics of ob/ob mice. The primary objective of this experiment was to investigate whether this altered leptin sensitivity in ob/ob mice was reflected in the hypothalamic mRNA profile. Research Methods and Procedures: Fifteen-week-old female ob/ob and lean mice were treated with 14 days of subcutaneous (sc) infusion of phosphate-buffered saline (PBS) or leptin (10 μg/d) using osmotic pumps. Real-time Taqman reverse transcription polymerase chain reaction (RT-PCR) (ABI Microfluidic cards) was used to quantitatively compare the mRNA levels of selected hypothalamic genes in these groups. Results: Hypothalamic mRNA levels for ob/ob control mice were higher for agouti-related protein (AGRP), neuropeptide Y (NPY), and arginine vasopressin (AVP), and lower for cocaine- and amphetamine-regulated transcript (CART), cAMP response element binding protein (CREB)-1, proopiomelanocortin (POMC)-1, and urocortin (UCN)-3 compared with lean controls. In leptin-treated ob/ob mice, hypothalamic mRNA levels were reduced for NPY, AGRP, AVP, and increased for suppressor of cytokine signaling 3 (SOCS3) compared with ob/ob controls. Leptin treatment dramatically up-regulated hypothalamic mRNA level of POMC1 in both lean and ob/ob mice. Strong correlations were observed between hypothalamic Janus kinase 2 (JAK2) and CREB1, STAT3 and CREB1, JAK2 and STAT3, NPY and AVP in all samples. Discussion: ob/ob and lean mice have different hypothalamic mRNA expression patterns (particularly those of feeding-related genes), and selected genes in ob/ob mice are more sensitive to exogenous leptin stimulation compared with lean mice.

Original languageEnglish (US)
Pages (from-to)2624-2633
Number of pages10
JournalObesity
Volume15
Issue number11
DOIs
Publication statusPublished - Nov 1 2007

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Keywords

  • Hypothalamic biomarkers
  • Lean mice
  • Leptin
  • Real-time reverse transcription polymerase chain reaction
  • ob/ob mice

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Nutrition and Dietetics

Cite this

Duan, J., Choi, Y. H., Hartzell, D., Della-Fera, M. A., Hamrick, M., & Baile, C. A. (2007). Effects of subcutaneous leptin injections on hypothalamic gene profiles in lean and ob/ob mice. Obesity, 15(11), 2624-2633. https://doi.org/10.1038/oby.2007.314