title: Interactions between leptin and hypothalamic neuropeptide Y neurons in the control of food intake and energy homeostasis in the rat.
abstract: Leptin acts on the brain to inhibit feeding, increase thermogenesis, and decrease body weight. Neuropeptide Y (NPY)-ergic neurons of the hypothalamic arcuate nucleus (ARC) that project to the paraventricular nuclei (PVN) and dorsomedial nuclei (DMH) are postulated to control energy balance by stimulating feeding and inhibiting thermogenesis, especially under conditions of energy deficit. We investigated whether leptin's short-term effects on energy balance are mediated by inhibition of the NPY neurons. Recombinant murine leptin (11 microg) injected into the lateral ventricle of fasted adult Wistar rats inhibited food intake by 20-25% between 2 and 6 h after administration, compared with saline-treated controls (P < 0.05). Uncoupling protein mRNA levels in brown adipose tissue (BAT) rose by 70% (P < 0.01). Leptin treatment significantly reduced NPY concentrations by 20-50% (P < 0.05) in the ARC, PVN, and DMH and significantly decreased hypothalamic NPY mRNA levels (0.61 +/- 0.02 vs. 0.78 +/- 0.03 arbitrary units; P < 0.01). A second study examined changes in leptin during 5 days' intracerebroventricular NPY administration (10 microg/day), which induced sustained hyperphagia and excessive weight gain. In NPY-treated rats, leptin mRNA levels in epididymal fat were comparable to those in saline-treated controls (0.94 +/- 0.17 vs. 1.0 +/- 0.28 arbitrary units; P > 0.1), but plasma leptin levels were significantly higher (4.88 +/- 0.66 vs. 2.85 +/- 0.20 ng/ml; P < 0.01). Leptin therefore acts centrally to decrease NPY synthesis and NPY levels in the ARC-PVN projection; reduced NPY release in the PVN may mediate leptin's hypophagic and thermogenic actions. Conversely, NPY-induced obesity results in raised circulating leptin concentrations. Leptin and the NPY-ergic ARC-PVN neurons may interact in a homeostatic loop to regulate body fat mass and energy balance.
authors.affiliation: Department of Medicine, The University of Liverpool, U.K.
authors.forename: Q
authors.initials: Q
authors.lastname: Wang
authors.forename: C
authors.initials: C
authors.lastname: Bing
authors.forename: K
authors.initials: K
authors.lastname: Al-Barazanji
authors.forename: D E
authors.initials: DE
authors.lastname: Mossakowaska
authors.forename: X M
authors.initials: XM
authors.lastname: Wang
authors.forename: D L
authors.initials: DL
authors.lastname: McBay
authors.forename: W A
authors.initials: WA
authors.lastname: Neville
authors.forename: M
authors.initials: M
authors.lastname: Taddayon
authors.forename: L
authors.initials: L
authors.lastname: Pickavance
authors.forename: S
authors.initials: S
authors.lastname: Dryden
authors.forename: M E
authors.initials: ME
authors.lastname: Thomas
authors.forename: M T
authors.initials: MT
authors.lastname: McHale
authors.forename: I S
authors.initials: IS
authors.lastname: Gloyer
authors.forename: S
authors.initials: S
authors.lastname: Wilson
authors.forename: R
authors.initials: R
authors.lastname: Buckingham
authors.forename: J R
authors.initials: JR
authors.lastname: Arch
authors.forename: P
authors.initials: P
authors.lastname: Trayhurn
authors.forename: G
authors.initials: G
authors.lastname: Williams
mesh_terms: D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis*; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D005247:Feeding Behavior / Q000187:drug effects*; D006963:Hyperphagia; D007031:Hypothalamus / Q000187:drug effects / Q000502:physiology*; D007263:Infusions, Parenteral; D007473:Ion Channels; D020738:Leptin; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D024101:Mitochondrial Proteins; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009478:Neuropeptide Y / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology*; D009765:Obesity; D015345:Oligonucleotide Probes; D014176:Protein Biosynthesis; D011506:Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects; D000071256:Uncoupling Protein 1; D015430:Weight Gain / Q000187:drug effects
chemical_list: D002352:Carrier Proteins; D007473:Ion Channels; D020738:Leptin; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D009478:Neuropeptide Y; D015345:Oligonucleotide Probes; D011506:Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D000071256:Uncoupling Protein 1