Neurochemical characterization of body weight-regulating leptin receptor neurons in the nucleus of the solitary tract.

Abstract

The action of peripherally released leptin at long-form leptin receptors (LepRb) within the brain represents a fundamental axis in the regulation of energy homeostasis and body weight. Efforts to delineate the neuronal mediators of leptin action have recently focused on extrahypothalamic populations and have revealed that leptin action within the nucleus of the solitary tract (NTS) is critical for normal appetite and body weight regulation. To elucidate the neuronal circuits that mediate leptin action within the NTS, we employed multiple transgenic reporter lines to characterize the neurochemical identity of LepRb-expressing NTS neurons. LepRb expression was not detected in energy balance-associated NTS neurons that express cocaine- and amphetamine-regulated transcript, brain-derived neurotrophic factor, neuropeptide Y, nesfatin, catecholamines, γ-aminobutyric acid, prolactin-releasing peptide, or nitric oxide synthase. The population of LepRb-expressing NTS neurons was comprised of subpopulations marked by a proopiomelanocortin-enhanced green fluorescent protein (EGFP) transgene and distinct populations that express proglucagon and/or cholecystokinin. The significance of leptin action on these three populations of NTS neurons was assessed in leptin-deficient Ob/Ob mice, revealing increased NTS proglucagon and cholecystokinin, but not proopiomelanocortin, expression. These data provide new insight into the appetitive brainstem circuits engaged by leptin.

• Authors: Alastair S Garfield, Christa Patterson, Susanne Skora, Fiona M Gribble, Frank Reimann, Mark L Evans, Martin G Myers Jr, Lora K Heisler
• Journal: Endocrinology (Endocrinology) Vol. 153 Issue 10 Pg. 4600-7 (Oct 2012) ISSN: 1945-7170 [Electronic] United States
• PMID: 22869346 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Brain-Derived Neurotrophic Factor
• Leptin
• Neuropeptide Y
• Prolactin-Releasing Hormone
• Receptors, Leptin
• STAT3 Transcription Factor
• Stat3 protein, mouse
• Proglucagon
• gamma-Aminobutyric Acid
• Pro-Opiomelanocortin
• Cholecystokinin

Topics

• Animals
• Body Weight (physiology)
• Brain-Derived Neurotrophic Factor (metabolism)
• Cholecystokinin (metabolism)
• Energy Metabolism (physiology)
• Leptin (metabolism)
• Mice
• Mice, Transgenic
• Neurons (metabolism)
• Neuropeptide Y (metabolism)
• Phosphorylation
• Pro-Opiomelanocortin (metabolism)
• Proglucagon (metabolism)
• Prolactin-Releasing Hormone (metabolism)
• Receptors, Leptin (metabolism)
• STAT3 Transcription Factor (metabolism)
• Solitary Nucleus (cytology, metabolism)
• gamma-Aminobutyric Acid (metabolism)