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Leptin in Brain Function

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Handbook of Neurochemistry and Molecular Neurobiology

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Abstract:

In the 21st century obesity affects around 25% of the population and is now one of the main contributors to ill health in Western societies. In recent years major advances have been made in identifying the key hormones that regulate food intake and body weight. In particular the cloning of the ob gene that encodes the endocrine peptide, leptin, has fueled a great deal of research into this area, and has established that this hormone plays a pivotal role in regulating energy balance via its actions in the hypothalamus. This in turn has greatly enhanced our understanding of the highly intricate neural systems within the hypothalamus that regulate energy homeostasis, and the complex interplay that exists between a range of orexigenic and anorexigenic agents (like leptin) to control this process. However, in addition to its fundamental role in regulating food intake and body weight, evidence is emerging that hypothalamic leptin receptors also play a key role in controlling reproductive function and bone formation. Moreover evidence is mounting that in addition to its hypothalamic actions, leptin has widespread actions in the CNS. Indeed in the hippocampus leptin is implicated in associative learning and memory processes as leptin‐receptor‐deficient rodents (db/db mice and fa/fa rats) display impairments in both long‐term potentiation (LTP) and long‐term depression (LTD), and in spatial memory tasks. Furthermore, at the cellular level, leptin has the capacity to convert hippocampal short‐term potentiation (STP) into LTP. There is also evidence that leptin, via its ability to modify the activity of specific potassium channels in the hippocampus, can regulate neuronal excitability. More recent studies indicate that the hormone leptin plays a key role in the development of the CNS. Indeed abnormal brain development has been reported in leptin‐deficient or insensitive rodents, and recent studies indicate that leptin actively participates in the development of the hypothalamus as specific arcuate nucleus projection pathways are permanently disrupted in ob/ob (leptin‐deficient) mice. In this chapter the recent advances made in leptin neurobiology are discussed. In particular the key role of leptin in regulating energy balance is addressed, together with the emerging evidence that this hormone play a fundamental role in numerous other CNS functions.

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Abbreviations

α‐MSH:

α melanocortin‐stimulating hormone

ARC:

arcuate nucleus

CART:

cocaine‐ and amphetamine‐regulated transcript

CIS:

cytokine inducible sequence

CNS:

central nervous system

db :

diabetes

IRS:

insulin receptor substrate

JAK:

janus tyrosine kinase

KATP :

ATP‐sensitive potassium channel

MAPK:

mitogen‐activated protein kinase

NPY:

neuropeptide Y

ob :

obese

ObR:

leptin receptor

PI‐3 kinase:

phosphoinositide‐3 kinase

POMC:

proopiomelanocortin

SOCS:

suppressor of cytokine signaling

STAT:

signal transducers and activators of transcription

VMH:

ventromedial hypothalamus

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  1. J. Harvey
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  1. Center for Neurochemistry, Nathan S. Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, 10962, Orangeburg, Newyork, USA

    Abel Lajtha (Director) (Director)

  2. Department of Neurology (Division of Neurochemistry and Neurobiology), University of Iowa College of Medicine and Veterans Administration Medical Center, 52242, lowa, lowa, USA

    Ramon Lim

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Harvey, J. (2006). Leptin in Brain Function. In: Lajtha, A., Lim, R. (eds) Handbook of Neurochemistry and Molecular Neurobiology. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-30381-9_28

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