Rhythmic, reciprocal ghrelin and leptin signaling: new insight in the development of obesity

The hypothalamus integrates metabolic, neural and hormonal signals to evoke an intermittent appetitive drive in the daily management of energy homeostasis. Three major players identified recently in the feedback communication between the periphery and hypothalamus are leptin, ghrelin and neuropeptid...

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Bibliographic Details
Published in:Regulatory Peptides 2003-03, Vol.111 (1), p.1-11
Main Authors: Kalra, Satya P, Bagnasco, Michela, Otukonyong, Effiong E, Dube, Michael G, Kalra, Pushpa S
Format: Article
Language:English
Subjects:
Activity Cycles - physiology
Adipocytes - metabolism
Animals
Biological and medical sciences
Circadian Rhythm - physiology
Circadian rhythms
Energy balance
Fasting - metabolism
Ghrelin
Growth Hormone - analysis
Growth Hormone - physiology
Humans
Hypothalamus
Hypothalamus - metabolism
Leptin - analysis
Leptin - physiology
Medical sciences
Metabolic diseases
Neuropeptide Y
Neuropeptide Y - metabolism
Obesity
Obesity - physiopathology
Peptide Hormones - analysis
Peptide Hormones - physiology
Signal Transduction - physiology
Ultradian rhythms
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Summary:The hypothalamus integrates metabolic, neural and hormonal signals to evoke an intermittent appetitive drive in the daily management of energy homeostasis. Three major players identified recently in the feedback communication between the periphery and hypothalamus are leptin, ghrelin and neuropeptide Y (NPY). We propose that reciprocal circadian and ultradian rhythmicities in the afferent humoral signals, anorexigenic leptin from adipocytes and orexigenic ghrelin from stomach, encode a corresponding discharge pattern in the appetite-stimulating neuropeptide Y network in the hypothalamus. An exquisitely intricate temporal relationship among these signaling modalities with varied sites of origin is paramount in sustenance of weight control on a daily basis. Our model envisages that subtle and progressive derangements in temporal communication, imposed by environmental shifts in energy intake, impel a positive energy balance culminating in excessive weight gain and obesity. This conceptual advance provides a new target for designing pharmacologic or gene transfer therapies that would normalize the rhythmic patterns of afferent hormonal and efferent neurochemical messages.
ISSN:0167-0115
1873-1686
DOI:10.1016/S0167-0115(02)00305-1