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Leptin Interaction with Brain Orexigenic and Anorexigenic Pathways

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Leptin

Abstract

The adipocyte hormone leptin exerts anorexigenic effects by acting on brain circuits that regulate food intake and energy expenditure. Our understanding of the mechanisms underlying leptin’s anorexigenic actions in the brain is derived mainly from studies on rodents. Primary targets of leptin’s anorexigenic action are NPY/AGRP and POMC neurons in the hypothalamus and whose projections convey leptin signaling to regions of the brain that influence food intake, reward-seeking behavior, arousal, and reproduction. Leptin’s anorexigenic effects involves enhancement of satiety signals to the nucleus of the solitary tract in the hindbrain, which receives neuronal projections arising from leptin responsive neurons in the hypothalamus. Obesity results from impaired leptin signaling to the brain as a consequence of leptin resistance, genetic or metabolic leptin deficiency, mutations of the leptin receptor gene or genes that impair the function of downstream leptin circuits in the brain, attenuated leptin receptor signal transduction, and brain inflammatory mechanisms. fMRI imaging studies suggest that similar mechanisms of leptin action operate in the human brain as has been established in rodent models of obesity.

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Abbreviations

ARC:

Arcuate nucleus

AGRP:

Agouti-related peptide

aMSH:

Alpha melanocyte stimulation hormone

CART:

Cocaine- and amphetamine-regulated transcript

CCK:

Cholecystokinin

CNS:

Central nervous system

CRH:

Corticotropin releasing hormone

CSF:

Cerebrospinal fluid

fMRI:

Functional magnetic resonance imaging

GABA:

Gamma amino butyric acid

JAK2:

Janus-activated kinase 2

Lep:

Leptin gene

LepR:

Leptin receptor

MAPK:

Mitogen-activated protein kinase

MCH:

Melanin concentrating hormone

MC4r:

Melanocortin 4 receptor

NMDR:

N-methyl-d-aspartate

NPY:

Neuropeptide Y

NTS:

Nucleus of the solitary tract

OXr:

Oxytocin receptor

PI3K:

Phosphatidylinositol 3-OH-kinase

POMC:

Proopiomelanocortin

PVN:

Paraventricular nucleus

STAT3:

Signal transducer and activator of transcription 3

Y1r:

Neuropeptide Y Y1 receptor

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Acknowledgements 

This material is based upon work supported by the Research and Development Service, Veterans Health Administration, Department of Veterans Affairs, and the Cellular and Molecular Imaging Core of the Diabetes Research Center at the University of Washington and supported by National Institutes of Health (NIH) grant P30DK017047. Dr. Baskin is the recipient of a VA Senior Research Career Scientist award.

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    Denis G. Baskin

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  1. Division of Endocrinology, Diabetes and Metabolism, University of Tennessee Health Science Center, Memphis, Tennessee, USA

    Sam Dagogo-Jack, MD

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Baskin, D.G. (2015). Leptin Interaction with Brain Orexigenic and Anorexigenic Pathways. In: Dagogo-Jack, MD, S. (eds) Leptin. Springer, Cham. https://doi.org/10.1007/978-3-319-09915-6_3

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-09914-9

  • Online ISBN: 978-3-319-09915-6

  • eBook Packages: MedicineMedicine (R0)

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