Leptin Does Not Directly Affect CNS Serotonin Neurons to Influence Appetite

• Published in: Cell metabolism Vol. 13; no. 5; pp. 584 - 591
• Main Authors: Lam, Daniel D., Leinninger, Gina M., Louis, Gwendolyn W., Garfield, Alastair S., Marston, Oliver J., Leshan, Rebecca L., Scheller, Erica L., Christensen, Lyndsay, Donato, Jose, Xia, Jing, Evans, Mark L., Elias, Carol, Dalley, Jeffrey W., Burdakov, Denis I., Myers, Martin G., Heisler, Lora K.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 04-05-2011
• Subjects: Adipose tissue; Animals; Appetite; Body weight; Body Weight - drug effects; Brain - cytology; Brain - drug effects; Brain - metabolism; Central nervous system; Electrophysiology; Energy balance; Hypothalamus - cytology; Hypothalamus - drug effects; Hypothalamus - metabolism; Immunoenzyme Techniques; Leptin - pharmacology; Leptin receptors; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Neural Pathways; Neurons; Neurons - cytology; Neurons - drug effects; Neurons - metabolism; Obesity - etiology; Obesity - metabolism; Receptors, Leptin - physiology; Serotonin; Serotonin - metabolism; Serotonin Plasma Membrane Transport Proteins - physiology
• ISSN: 1550-4131; 1932-7420
• DOI: 10.1016/j.cmet.2011.03.016

Serotonin (5-HT) and leptin play important roles in the modulation of energy balance. Here we investigated mechanisms by which leptin might interact with CNS 5-HT pathways to influence appetite. Although some leptin receptor (LepRb) neurons lie close to 5-HT neurons in the dorsal raphe (DR), 5-HT neurons do not express LepRb. Indeed, while leptin hyperpolarizes some non-5-HT DR neurons, leptin does not alter the activity of DR 5-HT neurons. Furthermore, 5-HT depletion does not impair the anorectic effects of leptin. The serotonin transporter-cre allele (Sert
cre) is expressed in 5-HT (and developmentally in some non-5-HT) neurons. While Sert
cre promotes LepRb excision in a few LepRb neurons in the hypothalamus, it is not active in DR LepRb neurons, and neuron-specific Sert
cre-mediated LepRb inactivation in mice does not alter body weight or adiposity. Thus, leptin does not directly influence 5-HT neurons and does not meaningfully modulate important appetite-related determinants via 5-HT neuron function.
► 5-HT neurons do not express leptin receptors and are not directly leptin responsive ► 5-HT depletion does not impair anorectic leptin action ► Sert
cre-mediated neuronal LepRb deletion does not affect DR leptin action, body weight, or adiposity ► Thus, leptin does not meaningfully influence appetite or body weight via brain 5-HT