Integrative physiology

Pflügers Archiv - European Journal of Physiology

, Volume 465, Issue 12, pp 1687-1699

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

  • Priscila CassollaAffiliated withDepartment of Physiology, School of Medicine of Ribeirão Preto, University of São Paulo
  • , Ernane Torres UchoaAffiliated withDepartment of Physiology, School of Medicine of Ribeirão Preto, University of São Paulo
  • , Frederico Sander Mansur MachadoAffiliated withDepartment of Physiology and Biophysics, Institute of Biological Sciences, Federal University of Minas Gerais
  • , Juliana Bohnen GuimarãesAffiliated withDepartment of Physiology and Biophysics, Institute of Biological Sciences, Federal University of Minas Gerais
  • , Maria Antonieta Rissato GarófaloAffiliated withDepartment of Physiology, School of Medicine of Ribeirão Preto, University of São Paulo
  • , Nilton de Almeida BritoAffiliated withDepartment of Physiological Sciences, Biological Sciences Center, State University of Maringá
  • , Lucila Leico Kagohara EliasAffiliated withDepartment of Physiology, School of Medicine of Ribeirão Preto, University of São Paulo
  • , Cândido Celso CoimbraAffiliated withDepartment of Physiology and Biophysics, Institute of Biological Sciences, Federal University of Minas Gerais
  • , Isis do Carmo KettelhutAffiliated withDepartment of Biochemistry and Immunology, School of Medicine of Ribeirão Preto, University of São Paulo
    • , Luiz Carlos Carvalho NavegantesAffiliated withDepartment of Physiology, School of Medicine of Ribeirão Preto, University of São Paulo Email author 

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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.

Keywords

Brown adipose tissue Fatty acid synthase inhibitors Thermogenesis Sympathetic activation