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Article ; Online: The hypothalamic ventral premammillary nucleus: A key site in leptin's regulation of reproduction.

Leshan, Rebecca L / Pfaff, Donald W

2014 Volume 61-62, Page(s) 239–247

Abstract: Reproduction is an energy-expensive process that relies on indicators of energy availability to adjust its proper functioning. The adipokine leptin provides one such metabolic signal, with leptin receptor-expressing neurons at sites widespread within the ...

Abstract	Reproduction is an energy-expensive process that relies on indicators of energy availability to adjust its proper functioning. The adipokine leptin provides one such metabolic signal, with leptin receptor-expressing neurons at sites widespread within the CNS, including regions associated with the neuroendocrine reproductive axis. One substantial population lies within the hypothalamic ventral premammillary nucleus (PMv), a region itself linked to reproductive control, which may provide a strategic site for the integration of energy availability, sensory and gonadal cues. Here we review our current understanding of leptin and PMv regulation of reproduction, including emerging details about intracellular mechanisms of leptin action at this site.
MeSH term(s)	Animals ; Humans ; Hypothalamus, Posterior/metabolism ; Leptin/metabolism ; Receptors, Leptin/metabolism ; Reproductive Physiological Phenomena
Chemical Substances	Leptin ; Receptors, Leptin
Language	English
Publishing date	2014-11
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	639443-7
ISSN	1873-6300 ; 0891-0618
ISSN (online)	1873-6300
ISSN	0891-0618
DOI	10.1016/j.jchemneu.2014.08.008
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Article ; Online: Molecular mapping of mouse brain regions innervated by leptin receptor-expressing cells.

Patterson, Christa M / Leshan, Rebecca L / Jones, Justin C / Myers, Martin G

Brain research

2011 Volume 1378, Page(s) 18–28

Abstract: Leptin acts via the long form of the leptin receptor (LepRb) on specialized sets of neurons in the brain to modulate diverse functions in concert with energy stores. Previous studies have revealed the distribution of LepRb-expressing neurons in the brain ...

Abstract	Leptin acts via the long form of the leptin receptor (LepRb) on specialized sets of neurons in the brain to modulate diverse functions in concert with energy stores. Previous studies have revealed the distribution of LepRb-expressing neurons in the brain but not the regions to which LepRb neurons project to mediate downstream leptin actions. We utilized LepRb-cre in combination with cre-inducible enhanced green fluorescent protein (EGFP) and farnesylated EGFP (EGFPf) mouse reporter strains to visualize LepRb neurons and their projections, respectively, throughout the brain. The areas containing LepRb soma and projections were relatively circumscribed, as many brain regions contained no detectable EGFP or EGFPf. The highest concentrations of LepRb neurons and LepRb projections were found in the hypothalamus, where the ventral premamillary (PMv), dorsomedial (DMH), and arcuate (ARC) nuclei contained the greatest number of cell bodies, in addition to substantial EGFPf-reactivity. Furthermore, both LepRb soma and projections were present in a few midbrain and brainstem nuclei. Several brain regions including the hypothalamic paraventricular nucleus (PVH), the anteroventral periventricular nucleus (AVPe), and the central nucleus of the amygdala (CeA) contained few LepRb neurons but substantial EGFPf, suggesting that these regions represent targets of LepRb neurons that lie elsewhere in the brain. In some nuclei that contained both soma and projections, the distribution of soma and projections differed, suggesting that these areas transmit leptin-encoded information in a neuroanatomically directional manner.
MeSH term(s)	Animals ; Brain/cytology ; Brain/metabolism ; Brain Mapping ; Female ; Mice ; Neural Pathways/cytology ; Neural Pathways/metabolism ; Receptors, Leptin/biosynthesis
Chemical Substances	Receptors, Leptin
Language	English
Publishing date	2011-01-13
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1200-2
ISSN	1872-6240 ; 0006-8993
ISSN (online)	1872-6240
ISSN	0006-8993
DOI	10.1016/j.brainres.2011.01.010
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Article ; Online: Leptin action through hypothalamic nitric oxide synthase-1-expressing neurons controls energy balance.

Leshan, Rebecca L / Greenwald-Yarnell, Megan / Patterson, Christa M / Gonzalez, Ian E / Myers, Martin G

Nature medicine

2012 Volume 18, Issue 5, Page(s) 820–823

Abstract: Few effective measures exist to combat the worldwide obesity epidemic(1), and the identification of potential therapeutic targets requires a deeper understanding of the mechanisms that control energy balance. Leptin, an adipocyte-derived hormone that ... ...

Abstract	Few effective measures exist to combat the worldwide obesity epidemic(1), and the identification of potential therapeutic targets requires a deeper understanding of the mechanisms that control energy balance. Leptin, an adipocyte-derived hormone that signals the long-term status of bodily energy stores, acts through multiple types of leptin receptor long isoform (LepRb)-expressing neurons (called here LepRb neurons) in the brain to control feeding, energy expenditure and endocrine function(2-4). The modest contributions to energy balance that are attributable to leptin action in many LepRb populations(5-9) suggest that other previously unidentified hypothalamic LepRb neurons have key roles in energy balance. Here we examine the role of LepRb in neuronal nitric oxide synthase (NOS1)-expressing LebRb (LepRb(NOS1)) neurons that comprise approximately 20% of the total hypothalamic LepRb neurons. Nos1(cre)-mediated genetic ablation of LepRb (Lepr(Nos1KO)) in mice produces hyperphagic obesity, decreased energy expenditure and hyperglycemia approaching that seen in whole-body LepRb-null mice. In contrast, the endocrine functions in Lepr(Nos1KO) mice are only modestly affected by the genetic ablation of LepRb in these neurons. Thus, hypothalamic LepRb(NOS1) neurons are a key site of action of the leptin-mediated control of systemic energy balance.
MeSH term(s)	Animals ; Energy Metabolism ; Hypothalamus/physiology ; Leptin/physiology ; Mice ; Neurons/physiology ; Nitric Oxide Synthase Type I/physiology ; Receptors, Leptin/physiology
Chemical Substances	Leptin ; Receptors, Leptin ; Nitric Oxide Synthase Type I (EC 1.14.13.39) ; Nos1 protein, mouse (EC 1.14.13.39)
Language	English
Publishing date	2012-04-20
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1220066-9
ISSN	1546-170X ; 1078-8956
ISSN (online)	1546-170X
ISSN	1078-8956
DOI	10.1038/nm.2724
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Zs.A 4212: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: The geometry of leptin action in the brain: more complicated than a simple ARC.

Myers, Martin G / Münzberg, Heike / Leinninger, Gina M / Leshan, Rebecca L

Cell metabolism

2009 Volume 9, Issue 2, Page(s) 117–123

Abstract: Leptin signals the repletion of fat stores, acting in the CNS to permit energy utilization by a host of autonomic and neuroendocrine processes and to decrease feeding. While much recent research has focused on the leptin-regulated circuitry of the ... ...

Abstract	Leptin signals the repletion of fat stores, acting in the CNS to permit energy utilization by a host of autonomic and neuroendocrine processes and to decrease feeding. While much recent research has focused on the leptin-regulated circuitry of the hypothalamic arcuate nucleus (ARC), the majority of brain leptin receptor (LepRb)-expressing neurons lie outside the ARC in other CNS regions known to modulate energy balance. Each set of LepRb neurons throughout the brain presumably mediates unique aspects of leptin action, and understanding the function for LepRb-expressing neurons throughout the brain represents a crucial next step in the study of energy homeostasis.
MeSH term(s)	Arcuate Nucleus of Hypothalamus/metabolism ; Brain/metabolism ; Central Nervous System ; Energy Metabolism ; Leptin/metabolism ; Neurons/metabolism ; Paraventricular Hypothalamic Nucleus/metabolism ; Receptors, Leptin/metabolism
Chemical Substances	Leptin ; Receptors, Leptin
Language	English
Publishing date	2009-02-03
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2176834-1
ISSN	1932-7420 ; 1550-4131
ISSN (online)	1932-7420
ISSN	1550-4131
DOI	10.1016/j.cmet.2008.12.001
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Article: Integration of stress and leptin signaling by CART producing neurons in the rodent midbrain centrally projecting Edinger-Westphal nucleus.

Xu, Lu / Janssen, Donny / van der Knaap, Noortje / Roubos, Eric W / Leshan, Rebecca L / Myers, Martin G / Gaszner, Balázs / Kozicz, Tamás

Frontiers in neuroanatomy

2014 Volume 8, Page(s) 8

Abstract: Leptin targets the brain to regulate feeding, neuroendocrine function and metabolism. The leptin receptor is present in hypothalamic centers controlling energy metabolism as well as in the centrally projecting Edinger-Westphal nucleus (EWcp), a region ... ...

Abstract	Leptin targets the brain to regulate feeding, neuroendocrine function and metabolism. The leptin receptor is present in hypothalamic centers controlling energy metabolism as well as in the centrally projecting Edinger-Westphal nucleus (EWcp), a region implicated in the stress response and in various aspects of stress-related behaviors. We hypothesized that the stress response by cocaine- and amphetamine-regulated transcript (CART)-producing EWcp-neurons would depend on the animal's energy state. To test this hypothesis, we investigated the effects of changes in energy state (mimicked by low, normal and high leptin levels, which were achieved by 24 h fasting, normal chow and leptin injection, respectively) on the response of CART neurons in the EWcp of rats subjected or not to acute restraint stress. Our data show that leptin treatment alone significantly increases CART mRNA expression in the rat EWcp and that in leptin receptor deficient (db/db) mice, the number of CART producing neurons in this nucleus is reduced. This suggests that leptin has a stimulatory effect on the production of CART in the EWcp under non-stressed condition. Under stressed condition, however, leptin blunts stress-induced activation of EWcp neurons and decreases their CART mRNA expression. Interestingly, fasting, does not influence the stress-induced activation of EWcp-neurons, and specifically EWcp-CART neurons are not activated. These results suggest that the stress response by the EWcp depends to some degree on the animal's energy state, a mechanism that may contribute to a better understanding of the complex interplay between obesity and stress.
Language	English
Publishing date	2014-03-03
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2452969-2
ISSN	1662-5129
ISSN	1662-5129
DOI	10.3389/fnana.2014.00008
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Article: Hitting the target: leptin and perinatal nutrition in the predisposition to obesity.

Myers, Martin G / Patti, Mary Elizabeth / Leshan, Rebecca L

Endocrinology

2005 Volume 146, Issue 10, Page(s) 4209–4210

MeSH term(s)	Animals ; Animals, Newborn ; Diet ; Genetic Predisposition to Disease ; Humans ; Leptin/physiology ; Obesity/epidemiology ; Obesity/genetics ; Rats ; Rats, Wistar ; United States ; Weight Gain
Chemical Substances	Leptin
Language	English
Publishing date	2005-10
Publishing country	United States
Document type	Comment ; News
ZDB-ID	427856-2
ISSN	1945-7170 ; 0013-7227
ISSN (online)	1945-7170
ISSN	0013-7227
DOI	10.1210/en.2005-0971
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Article: Leptin receptor signaling and action in the central nervous system.

Leshan, Rebecca L / Björnholm, Marie / Münzberg, Heike / Myers, Martin G

Obesity (Silver Spring, Md.)

2006 Volume 14 Suppl 5, Page(s) 208S–212S

Abstract: The increasing incidence of obesity in developed nations represents an ever-growing challenge to health care by promoting diabetes and other diseases. The discovery of the hormone, leptin, a decade ago has facilitated the acquisition of new knowledge ... ...

Abstract	The increasing incidence of obesity in developed nations represents an ever-growing challenge to health care by promoting diabetes and other diseases. The discovery of the hormone, leptin, a decade ago has facilitated the acquisition of new knowledge regarding the regulation of energy balance. A great deal remains to be discovered regarding the molecular and anatomic actions of leptin, however. Here, we discuss the mechanisms by which leptin activates intracellular signals, the roles that these signals play in leptin action in vivo, and sites of leptin action in vivo. Using "reporter" mice, in which LRb-expressing (long form of the leptin receptor) neurons express the histological marker, beta-galactosidase, coupled with the detection of LRb-mediated signal transducer and activator of transcription 3 signaling events, we identified LRb expression in neuronal populations both within and outside the hypothalamus. Understanding the regulation and physiological function of these myriad sites of central leptin action will be a crucial next step in the quest to understand mechanisms of leptin action and energy balance.
MeSH term(s)	Animals ; Central Nervous System/physiology ; Energy Metabolism/physiology ; Gene Expression ; Homeostasis/physiology ; Humans ; Leptin/physiology ; Mice ; Mice, Transgenic ; Multienzyme Complexes ; Neurons/physiology ; Obesity/etiology ; Obesity/metabolism ; Receptors, Cell Surface/metabolism ; Receptors, Leptin ; Signal Transduction
Chemical Substances	LEPR protein, human ; Leptin ; Multienzyme Complexes ; Receptors, Cell Surface ; Receptors, Leptin ; leptin receptor, mouse
Language	English
Publishing date	2006-09-28
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2230457-5
ISSN	1930-739X ; 1930-7381 ; 1071-7323
ISSN (online)	1930-739X
ISSN	1930-7381 ; 1071-7323
DOI	10.1038/oby.2006.310
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Article: Molecular mapping of mouse brain regions innervated by leptin receptor-expressing cells

Patterson, Christa M / Leshan, Rebecca L / Jones, Justin C / Myers, Martin G., Jr

Brain research. 2011 Mar. 10, v. 1378

2011

Abstract	Leptin acts via the long form of the leptin receptor (LepRb) on specialized sets of neurons in the brain to modulate diverse functions in concert with energy stores. Previous studies have revealed the distribution of LepRb-expressing neurons in the brain but not the regions to which LepRb neurons project to mediate downstream leptin actions. We utilized LepRb-cre in combination with cre-inducible enhanced green fluorescent protein (EGFP) and farnesylated EGFP (EGFPf) mouse reporter strains to visualize LepRb neurons and their projections, respectively, throughout the brain. The areas containing LepRb soma and projections were relatively circumscribed, as many brain regions contained no detectable EGFP or EGFPf. The highest concentrations of LepRb neurons and LepRb projections were found in the hypothalamus, where the ventral premamillary (PMv), dorsomedial (DMH), and arcuate (ARC) nuclei contained the greatest number of cell bodies, in addition to substantial EGFPf-reactivity. Furthermore, both LepRb soma and projections were present in a few midbrain and brainstem nuclei. Several brain regions including the hypothalamic paraventricular nucleus (PVH), the anteroventral periventricular nucleus (AVPe), and the central nucleus of the amygdala (CeA) contained few LepRb neurons but substantial EGFPf, suggesting that these regions represent targets of LepRb neurons that lie elsewhere in the brain. In some nuclei that contained both soma and projections, the distribution of soma and projections differed, suggesting that these areas transmit leptin-encoded information in a neuroanatomically directional manner.
Keywords	amygdala ; brain stem ; chromosome mapping ; energy ; green fluorescent protein ; leptin ; leptin receptors ; mice ; neurons ; paraventricular hypothalamic nucleus
Language	English
Dates of publication	2011-0310
Size	p. 18-28.
Publishing place	Elsevier B.V.
Document type	Article
ZDB-ID	1200-2
ISSN	1872-6240 ; 0006-8993
ISSN (online)	1872-6240
ISSN	0006-8993
DOI	10.1016/j.brainres.2011.01.010
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Article: Leptin Receptor Signaling and Action in the Central Nervous System

Leshan, Rebecca L / Björnholm, Marie / Münzberg, Heike / Myers, Martin G. Jr

Obesity. 2006 Aug., v. 14, Suppl. 005

2006

Abstract	The increasing incidence of obesity in developed nations represents an ever-growing challenge to health care by promoting diabetes and other diseases. The discovery of the hormone, leptin, a decade ago has facilitated the acquisition of new knowledge regarding the regulation of energy balance. A great deal remains to be discovered regarding the molecular and anatomic actions of leptin, however. Here, we discuss the mechanisms by which leptin activates intracellular signals, the roles that these signals play in leptin action in vivo, and sites of leptin action in vivo. Using "reporter" mice, in which LRb-expressing (long form of the leptin receptor) neurons express the histological marker, β-galactosidase, coupled with the detection of LRb-mediated signal transducer and activator of transcription 3 signaling events, we identified LRb expression in neuronal populations both within and outside the hypothalamus. Understanding the regulation and physiological function of these myriad sites of central leptin action will be a crucial next step in the quest to understand mechanisms of leptin action and energy balance.
Keywords	leptin ; hormone receptors ; central nervous system ; obesity ; mice ; animal models ; histology ; beta-galactosidase ; hypothalamus ; energy balance
Language	English
Dates of publication	2006-08
Size	p. 208S-212S.
Publishing place	The North American Association for the Study of Obesity
Document type	Article
Note	In the special issue: The neurobiology of obesity / edited by D. Richard and P. Boisvert. Paper presented at a symposium held on November 4-5, 2005, in Quebec City, Quebec, Canada.
ZDB-ID	1201744-9
ISSN	1550-8528 ; 1071-7323
ISSN (online)	1550-8528
ISSN	1071-7323
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Ventral tegmental area leptin receptor neurons specifically project to and regulate cocaine- and amphetamine-regulated transcript neurons of the extended central amygdala.

Leshan, Rebecca L / Opland, Darren M / Louis, Gwendolyn W / Leinninger, Gina M / Patterson, Christa M / Rhodes, Christopher J / Münzberg, Heike / Myers, Martin G

The Journal of neuroscience : the official journal of the Society for Neuroscience

2010 Volume 30, Issue 16, Page(s) 5713–5723

Abstract: Leptin acts via its receptor (LepRb) to regulate neural circuits in concert with body energy stores. In addition to acting on a number of hypothalamic structures, leptin modulates the mesolimbic dopamine (DA) system. To determine the sites at which LepRb ...

Abstract	Leptin acts via its receptor (LepRb) to regulate neural circuits in concert with body energy stores. In addition to acting on a number of hypothalamic structures, leptin modulates the mesolimbic dopamine (DA) system. To determine the sites at which LepRb neurons might directly influence the mesolimbic DA system, we examined the distribution of LepRb neurons and their projections within mesolimbic brain regions. Although the ventral tegmental area (VTA) contains DA LepRb neurons, LepRb neurons are absent from the amygdala and striatum. Also, LepRb-EGFPf mice (which label projections from LepRb neurons throughout the brain) reveal that few LepRb neurons project to the nucleus accumbens (NAc). In contrast, the central amygdala (CeA) and its rostral extension receive copious projections from LepRb neurons. Indeed, LepRb-specific anterograde tracing demonstrates (and retrograde tracing confirms) that VTA LepRb neurons project to the extended CeA (extCeA) but not the NAc. Consistently, leptin promotes cAMP response element-binding protein phosphorylation in the extCeA, but not NAc, of leptin-deficient animals. Furthermore, transgenic mice expressing the trans-synaptic tracer wheat germ agglutinin in LepRb neurons reveal the innervation of CeA cocaine- and amphetamine-regulated transcript (CART) neurons by LepRb neurons, and leptin suppresses the increased CeA CART expression of leptin-deficient animals. Thus, LepRb VTA neurons represent a subclass of VTA DA neurons that specifically innervates and controls the extCeA; we hypothesize that these neurons primarily modulate CeA-directed behaviors.
MeSH term(s)	Amphetamine/analysis ; Amygdala/chemistry ; Amygdala/physiology ; Animals ; Cocaine/analysis ; Mice ; Mice, Obese ; Mice, Transgenic ; Neural Pathways/chemistry ; Neural Pathways/physiology ; Neurons/chemistry ; Neurons/classification ; Neurons/physiology ; Receptors, Leptin/analysis ; Receptors, Leptin/physiology ; Transcription, Genetic/physiology ; Ventral Tegmental Area/chemistry ; Ventral Tegmental Area/physiology
Chemical Substances	Receptors, Leptin ; Amphetamine (CK833KGX7E) ; Cocaine (I5Y540LHVR)
Language	English
Publishing date	2010-04-21
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	604637-x
ISSN	1529-2401 ; 0270-6474
ISSN (online)	1529-2401
ISSN	0270-6474
DOI	10.1523/JNEUROSCI.1001-10.2010
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