title: Rhythmic, reciprocal ghrelin and leptin signaling: new insight in the development of obesity.
abstract: 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.
authors.affiliation: Department of Neuroscience, College of Medicine, University of Florida McKnight Brain Institute, PO Box 100244, Gainesville, FL 32610-0244, USA. skalra@ufbi.ufl.edu
authors.forename: Satya P
authors.initials: SP
authors.lastname: Kalra
authors.forename: Michela
authors.initials: M
authors.lastname: Bagnasco
authors.forename: Effiong E
authors.initials: EE
authors.lastname: Otukonyong
authors.forename: Michael G
authors.initials: MG
authors.lastname: Dube
authors.forename: Pushpa S
authors.initials: PS
authors.lastname: Kalra
mesh_terms: D000204:Activity Cycles / Q000502:physiology; D017667:Adipocytes / Q000378:metabolism; D000818:Animals; D002940:Circadian Rhythm / Q000502:physiology*; D005215:Fasting / Q000378:metabolism; D054439:Ghrelin; D013006:Growth Hormone / Q000032:analysis / Q000502:physiology; D006801:Humans; D007031:Hypothalamus / Q000378:metabolism; D020738:Leptin / Q000032:analysis / Q000502:physiology*; D009478:Neuropeptide Y / Q000378:metabolism; D009765:Obesity / Q000503:physiopathology*; D036361:Peptide Hormones / Q000032:analysis / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D054439:Ghrelin; D020738:Leptin; D009478:Neuropeptide Y; D036361:Peptide Hormones; D013006:Growth Hormone