Intrauterine food restriction alters the expression of uncoupling proteins in brown adipose tissue of rat newborns Thais L.V. Souza a , Carolina T. Coelho a , Paola B. Guimar ~ aes a , Eduardo M. Goto b , Sylvia Maria A. Silva a , Jose ´ Antonio Silva Jr c , Maria Tereza Nunes d , Silvia S.M. Ihara b , Jacqueline Luz a,n a Department of Physiology, Universidade Federal de S ~ ao Paulo, Rua Botucatu, 862 – 5th floor – CEP: 04023-900, Brazil b Department of Pathology, Universidade Federal de S ~ ao Paulo, Rua Botucatu, 740 – CEP: 04023-900, Brazil c Department of Rehabilitation Science, Universidade Nove de Julho, UNINOVE, Brazil, Av. Francisco Matarazzo, 612 – 1st floor – CEP: 05001-100, Brazil d Department of Physiology and Biophysics, Universidade de S ~ ao Paulo, Brazil, Av. Dr. Lineu Prestes, 1524 – CEP: 05508-000, Brazil article info Article history: Received 19 August 2011 Accepted 8 December 2011 Available online 16 December 2011 Keywords: Body temperature Maternal food restriction Undernutrition Thermoregulation Uncoupling proteins abstract A previous study from our laboratory showed that maternal food restriction (MFR) delays thermo- regulation in newborn rats. In neonates brown adipose tissue (BAT) is essential for thermogenesis due to the presence of uncoupling proteins (UCPs). The aim of this study was to evaluate the influence of MFR on the UCPs mRNA and protein expression in BAT and skeletal muscle (SM) of the newborn rat. Female Wistar EPM-1 control rats (CON) received chow ad libitum during pregnancy, whereas food- restricted dams (RES) received 50% of the amount ingested by CON. Fifteen hours after birth, the litters were weighed and sacrificed. Blood was collected for hormonal analysis. BAT and SM were used for determination of UCPs mRNA and protein expression, and Ca 2 þ -ATPase sarcoplasmic reticulum (SERCA1). RES pups showed a significant reduction in body weight and fat content at birth. MFR caused a significant increase in the expression of UCP1 and UCP2 in BAT, without changes in UCP3 and SERCA1 expression in BAT and SM. No differences between groups were found for leptin, T4 and glucose levels. RES pups showed increased insulin and decreased T3 levels. The delay in development of thermoregulation previously described in RES animals appears not to result from impairment in thermogenesis, but from an increase in heat loss, since MFR caused low birth weight in pups, leading to greater surface/volume ratio. The higher expression of UCP1 and UCP2 in BAT suggests a compensatory mechanism to increased thermogenesis. & 2011 Elsevier Ltd. All rights reserved. 1. Introduction During pregnancy maternal nutrition plays a pivotal role in the regulation of fetal and placental development. Barker (1991) showed that many adult diseases, including degenerative ones, are the consequence of inadequate pre- and pos-natal life condi- tions. Food restriction imposed during pregnancy usually leads to alterations in fetal development (Fowden and Forhead, 2004). Numerous factors can cause intrauterine growth restriction (Rosenberg, 2008), most of which resulting in adult sequelae (Ross and Beall, 2008). Fetal growth is a complex and dynamic process that occurs in the uterus, which provides a relatively stable thermal environ- ment. In contrast to fetuses, the neonate produces extra heat to compensate the loss that occurs at birth. The thermogenic response begins within minutes after birth and continues for many hours being, essentially mediated by the brown adipose tissue (BAT), which is the main source of heat production in the newborn (Gordon, 1993; Carmona et al., 1998; Asakura, 2004). The thermogenic capacity of BAT is mediated by uncoupling protein 1 (UCP1) present in the inner mitochondrial membrane (Himms-Hagen, 1985). Innervation of BAT by the sympathetic nervous system is largely known and its activation is the main stimulator of BAT-related thermogenesis (Bartness et al., 2010), as well as brown adipocytes differentiation, development and activ- ity (Richard et al., 2010; Richard and Picard, 2011). Mitochondrial uncoupling proteins (UCPs) are related to main- tenance of metabolic rate and adaptive thermoregulation (Jez ˇek, 2002). UCP1 is the responsible for non-shivering thermogenesis in the neonate and belongs to a family of UCPs, including UCP2 and UCP3, all expressed in BAT (Ledesma et al., 2002; Divakaruni and Brand, 2011). Ca 2þ -ATPase sarcoplasmic reticulum (SERCA1), found in skeletal muscle (SM), is another protein associated with heat production and it also was recently described in BAT (De Me ´ is, 2003). Nazarova (Nazarova, 1993) has shown that growth restricted newborns by reduction of uterine-placental flux are unable Contents lists available at SciVerse ScienceDirect journal homepage: www.elsevier.com/locate/jtherbio Journal of Thermal Biology 0306-4565/$ - see front matter & 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.jtherbio.2011.12.002 n Corresponding author. Tel.: þ55 11 5576 4511; fax: þ55 11 5575 9165. E-mail address: jluz@unifesp.br (J. Luz). Journal of Thermal Biology 37 (2012) 138–143