The Anorectic Effect of CNTF Does Not Require Action in Leptin-Responsive Neurons

• Published in: Endocrinology (Philadelphia) Vol. 153; no. 6; pp. 2647 - 2654
• Main Authors: Stefater, M. A, MacLennan, A. J, Lee, N, Patterson, C. M, Haller, A, Sorrell, J, Myers, M, Woods, S. C, Seeley, R. J
• Format: Journal Article
• Language: English
• Published: Chevy Chase, MD Endocrine Society 01.06.2012
• Subjects: Animals; Appetite Depressants - pharmacology; Biological and medical sciences; Body Weight - drug effects; Ciliary Neurotrophic Factor - pharmacology; Ciliary Neurotrophic Factor Receptor alpha Subunit - genetics; Ciliary Neurotrophic Factor Receptor alpha Subunit - metabolism; Diet, High-Fat; Eating - drug effects; Energy Balance-Obesity; Energy Metabolism - drug effects; Female; Fundamental and applied biological sciences. Psychology; Immunohistochemistry; Leptin - pharmacology; Male; Mice; Mice, Knockout; Mice, Transgenic; Neurons - drug effects; Neurons - metabolism; Paraventricular Hypothalamic Nucleus - cytology; Paraventricular Hypothalamic Nucleus - drug effects; Paraventricular Hypothalamic Nucleus - metabolism; Phosphorylation - drug effects; Receptors, Leptin - genetics; Receptors, Leptin - metabolism; Signal Transduction - drug effects; STAT3 Transcription Factor - metabolism; Vertebrates: endocrinology; Neuron; Adipokine; Anorectic; Ciliary neurotrophic factor; Leptin
• ISSN: 0013-7227; 1945-7170
• DOI: 10.1210/en.2012-1024

Leptin resistance is a feature of obesity that poses a significant therapeutic challenge. Any treatment that is effective to reduce body weight in obese patients must overcome or circumvent leptin resistance, which promotes the maintenance of excess body fat in obese individuals. Ciliary neurotrophic factor (CNTF) is unique in its ability to reduce food intake and body weight in obese, leptin-resistant humans and rodents. Although attempts to use CNTF as an obesity therapy failed due to the development of neutralizing antibodies to the drug, efforts to understand mechanisms for CNTF's anorectic effects provide an opportunity to develop new drugs for leptin-resistant individuals. CNTF and leptin share several structural, anatomic, and signaling properties, but it is not understood whether or how the two cytokines might interact to affect energy balance. Here, we conditionally deleted the CNTF receptor (CNTFR) subunit, CNTFRα, in cells expressing leptin receptors. We found that CNTFR signaling in leptin-responsive neurons is not required for endogenous maintenance of energy balance and is not required for the anorectic response to exogenous administration of a CNTF agonist. These results indicate that despite anatomical overlap for CNTF and leptin action, CNTF appears to act within a distinct neuronal population to elicit its potent anorectic effect.