title: The central administration of C75, a fatty acid synthase inhibitor, activates sympathetic outflow and thermogenesis in interscapular brown adipose tissue.
abstract: The present work investigated the participation of interscapular brown adipose tissue (IBAT), which is an important site for thermogenesis, in the anti-obesity effects of C75, a synthetic inhibitor of fatty acid synthase (FAS). We report that a single intracerebroventricular (i.c.v.) injection of C75 induced hypophagia and weight loss in fasted male Wistar rats. Furthermore, C75 induced a rapid increase in core body temperature and an increase in heat dissipation. In parallel, C75 stimulated IBAT thermogenesis, which was evidenced by a marked increase in the IBAT temperature that preceded the rise in the core body temperature and an increase in the mRNA levels of uncoupling protein-1. As with C75, an i.c.v. injection of cerulenin, a natural FAS inhibitor, increased the core body and IBAT temperatures. The sympathetic IBAT denervation attenuated all of the thermoregulatory effects of FAS inhibitors as well as the C75 effect on weight loss and hypophagia. C75 induced the expression of Fos in the paraventricular nucleus, preoptic area, dorsomedial nucleus, ventromedial nucleus, and raphé pallidus, all of which support a central role of FAS in regulating IBAT thermogenesis. These data indicate a role for IBAT in the increase in body temperature and hypophagia that is induced by FAS inhibitors and suggest new mechanisms explaining the weight loss induced by these compounds.
authors.affiliation: Department of Physiology, School of Medicine of Ribeirão Preto, University of São Paulo, 3900 Bandeirantes Avenue, Ribeirão Preto, São Paulo, 14049-900, Brazil.
authors.forename: Priscila
authors.initials: P
authors.lastname: Cassolla
authors.forename: Ernane Torres
authors.initials: ET
authors.lastname: Uchoa
authors.forename: Frederico Sander
authors.initials: FS
authors.lastname: Mansur Machado
authors.forename: Juliana Bohnen
authors.initials: JB
authors.lastname: Guimarães
authors.forename: Maria Antonieta
authors.initials: MA
authors.lastname: Rissato Garófalo
authors.forename: Nilton
authors.initials: N
authors.lastname: de Almeida Brito
authors.forename: Lucila Leico
authors.initials: LL
authors.lastname: Kagohara Elias
authors.forename: Cândido Celso
authors.initials: CC
authors.lastname: Coimbra
authors.forename: Isis
authors.initials: I
authors.lastname: do Carmo Kettelhut
authors.forename: Luiz Carlos
authors.initials: LC
authors.lastname: Carvalho Navegantes
mesh_terms: D015107:4-Butyrolactone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D002001:Adipose Tissue, Brown / Q000187:drug effects* / Q000294:innervation / Q000502:physiology; D000818:Animals; D004435:Eating / Q000187:drug effects; D054890:Fatty Acid Synthase, Type I / Q000037:antagonists & inhibitors*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012881:Skin Temperature / Q000187:drug effects; D013562:Sympathectomy; D022722:Thermogenesis / Q000187:drug effects*
chemical_list: C406734:4-methylene-2-octyl-5-oxofuran-3-carboxylic acid; D054890:Fatty Acid Synthase, Type I; D015107:4-Butyrolactone