The central administration of C75, a fatty acid synthase inhibitor, activates sympathetic outflow and thermogenesis in interscapular brown adipose tissue

Author(s)

Cassolla, Priscila ^[1] ; Uchoa, Ernane Torres ^[1] ; Mansur Machado, Frederico Sander ^[2] ; Guimaraes, Juliana Bohnen ^[2] ; Rissato Garofalo, Maria Antonieta ^[1] ; Brito, Nilton de Almeida ^[3] ; Kagohara Elias, Lucila Leico ^[1] ; Coimbra, Candido Celso ^[2] ; Kettelhut, Isis do Carmo ^[4] ; Carvalho Navegantes, Luiz Carlos ^[1]

Affiliation

^[1] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Physiol, BR-14049900 Ribeirao Preto, SP - Brazil

^[2] Univ Fed Minas Gerais, Inst Biol Sci, Dept Physiol & Biophys, BR-31270901 Belo Horizonte, MG - Brazil

^[3] Univ Estadual Maringa, Ctr Biol Sci, Dept Physiol Sci, BR-87020900 Maringa, Parana - Brazil

^[4] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Biochem & Immunol, BR-14049900 Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY; v. 465, n. 12, p. 1687-1699, DEC 2013.
• Web of Science Citations: 2

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 raph, 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. (AU)

• FAPESP's process: 08/06694-6 - Neural control of protein metabolism
• Grantee: Isis Do Carmo Kettelhut
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 09/07584-2 - Role of signaling pathways Akt/Foxo and MEK/ERK on anti-atrophic effect induced by adrenoceptors-B2 in rat skeletal muscle
• Grantee: Dawit Albieiro Pinheiro Gonçalves
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 10/11015-0 - Intracellular mechanisms involved in anticatabolic effect of the epinephrine in skeletal muscle of fasted rats
• Grantee: Flávia Aparecida Graça
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 10/11083-6 - ROLE OF EPAC IN CONTROL OF PROTEIN METABOLISM IN SKELETAL MUSCLE
• Grantee: Wilian de Assis Silveira
• Support Opportunities: Scholarships in Brazil - Doctorate