title: Sympathetic inhibition, leptin, and uncoupling protein subtype expression in normal fasting rats.
abstract: To further investigate neural effects on leptin and uncoupling proteins (UCPs), we studied in vivo perturbations intended to block adrenergic input to peripheral tissues. We examined plasma leptin, leptin mRNA, and adipose and muscle UCP subtype mRNA in rats treated with alpha-methyl-p-tyrosine methyl ester (AMPT-ME), which inhibits catecholamine synthesis and 6-hydroxydopamine (6HDA), which is toxic to catecholinergic nerve terminals but, unlike AMPT-ME, does not enter the central nervous system. Intraperitoneal AMPT-ME, 250 mg/kg, was administered at 1800 and 0700 the following day, and rats were killed at 1200-1400. All rats were fasted with free access to water during this time. Intraperitoneal AMPT-ME increased plasma leptin by 15-fold, increased interscapular brown adipose tissue (IBAT) and epididymal fat leptin mRNA by 2- to 2.5-fold, and also increased plasma insulin and glucose concentrations. Intraperitoneal AMPT-ME decreased IBAT UCP-3 mRNA to 40% of control, while it increased epididymal adipose UCP-3 mRNA approximately twofold. Intravenous AMPT-ME, 250 mg/kg, administered to conscious rats for 5 h decreased lumbar sympathetic nerve activity, increased plasma leptin (5.89 +/- 1.43 compared with 2.75 +/- 0.31 ng/ml in vehicle-treated rats, n = 7, P < 0.05), and decreased cardiac rate with no sustained change in blood pressure. Intraperitoneal 6HDA, 100 mg/kg, as a single dose at 1800, increased plasma leptin approximately twofold after 18-20 h, increased IBAT (but not epididymal fat) leptin mRNA by two- to threefold, and decreased IBAT UCP-3 mRNA to 30-40% of control. Neither AMPT-ME nor 6HDA significantly altered mRNA encoding gastrocnemius muscle UCP-3, IBAT UCP-1, or IBAT and epididymal UCP-2. In summary, AMPT-ME and 6HDA increased plasma leptin and upregulated leptin mRNA expression. AMPT-ME also resulted in complex tissue and subtype-specific modulation of adipose UCP mRNA. These data are consistent with interaction between leptin and sympathetic nerve activity (SNA) in regulation of fat cell energy utilization. However, the in vivo modulation of leptin and UCPs appears complex and, beyond a causal effect of SNA per se, may depend on concurrent changes in plasma insulin, glucose, and circulatory hemodynamics.
authors.affiliation: Department of Internal Medicine, Division of Adult and Pediatric Endocrinology, University of Iowa, Iowa City, Iowa 52246, USA. William-Sivitz@uiowa.edu
authors.forename: W I
authors.initials: WI
authors.lastname: Sivitz
authors.forename: B D
authors.initials: BD
authors.lastname: Fink
authors.forename: D A
authors.initials: DA
authors.lastname: Morgan
authors.forename: J M
authors.initials: JM
authors.lastname: Fox
authors.forename: P A
authors.initials: PA
authors.lastname: Donohoue
authors.forename: W G
authors.initials: WG
authors.lastname: Haynes
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D018663:Adrenergic Agents / Q000494:pharmacology; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D005215:Fasting / Q000502:physiology*; D007473:Ion Channels; D020738:Leptin / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D008781:Methyltyrosines / Q000494:pharmacology; D024101:Mitochondrial Proteins; D009433:Neural Inhibition / Q000502:physiology*; D016627:Oxidopamine / Q000494:pharmacology; D020033:Protein Isoforms / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D013564:Sympathetic Nervous System / Q000502:physiology*; D000071256:Uncoupling Protein 1
chemical_list: D018663:Adrenergic Agents; D002352:Carrier Proteins; D007473:Ion Channels; D020738:Leptin; D008565:Membrane Proteins; D008781:Methyltyrosines; D024101:Mitochondrial Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; C000604373:Ucp1 protein, rat; D000071256:Uncoupling Protein 1; C022260:alpha-methyltyrosine methyl ester; D016627:Oxidopamine