Effects of Subcutaneous Leptin Injections on Hypothalamic Gene Profiles in Lean and ob/ob Mice

• Published in: Obesity (Silver Spring, Md.) Md.), 2007-11, Vol.15 (11), p.2624-2633
• Main Authors: Duan, Jiuhua, Choi, Yang‐Ho, Hartzell, Diane, Della‐Fera, Mary Anne, Hamrick, Mark, Baile, Clifton A.
• Format: Article
• Language: English
• Subjects: Animals; Arginine Vasopressin - genetics; Arginine Vasopressin - metabolism; Body Weight - genetics; Cyclic AMP Response Element-Binding Protein - genetics; Cyclic AMP Response Element-Binding Protein - metabolism; Disease Models, Animal; Eating - genetics; Female; Gene Expression Profiling; hypothalamic biomarkers; Hypothalamus - drug effects; Hypothalamus - metabolism; Injections, Subcutaneous; Janus Kinase 2 - genetics; Janus Kinase 2 - metabolism; lean mice; leptin; Leptin - administration & dosage; Leptin - metabolism; Leptin - pharmacology; Mice; Mice, Obese; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Neuropeptide Y - genetics; Neuropeptide Y - metabolism; ob/ob mice; Obesity - metabolism; Pro-Opiomelanocortin - genetics; Pro-Opiomelanocortin - metabolism; real‐time reverse transcription polymerase chain reaction; RNA, Messenger - metabolism; STAT3 Transcription Factor - genetics; STAT3 Transcription Factor - metabolism; Suppressor of Cytokine Signaling 3 Protein; Suppressor of Cytokine Signaling Proteins - genetics; Suppressor of Cytokine Signaling Proteins - metabolism; Thinness - metabolism; Urocortins - genetics; Urocortins - metabolism
• ISSN: 1930-7381; 1930-739X
• DOI: 10.1038/oby.2007.314

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.