Research Report Consequences of metabolic challenges on hypothalamic colipase and PLRP2 mRNA in rats Catarina Rippe, Charlotte Erlanson-Albertsson, Andreas Lindqvist ⁎ Department of Experimental Medical Science, BMC, B11, 221 84 Lund, Sweden ARTICLE INFO ABSTRACT Article history: Accepted 12 September 2007 Available online 20 September 2007 The hypothalamus is the main appetite-regulating center in the brain receiving peripheral signals regarding the metabolic status of the body. Pancreatic procolipase has recently been identified in rat hypothalamus. Procolipase is known mainly for its actions in the intestine where it is cleaved to colipase, an enzyme required for the maintenance of pancreatic lipase activity, and enterostatin, a peptide involved in appetite regulation through the gut–brain axis. Colipase is able to increase the activity of pancreatic lipase- related protein-2 (PLRP2), a lipase also expressed in extra-pancreatic tissues. This study was performed to elucidate if PLRP2, in addition to colipase, is expressed in the hypothalamus and if the mRNAs of colipase and PLRP2 respond to metabolic challenges such as fasting, high-fat feeding or feeding sugar solutions. RNA from rat hypothalamus was extracted and subjected to RT-PCR. For quantitative mRNA analysis of hypothalamic tissue from the different metabolic situations real-time RT-PCR was used. We found PLRP2 and colipase mRNA to be expressed in the hypothalamus. An overnight fast resulted in down-regulated colipase (3-fold) and PLRP2 (7-fold) mRNA compared to freely fed rats. Conversely, high-fat feeding resulted in up-regulated colipase and PLRP2 mRNA (1.3-fold and 1.8-fold, respectively) compared to standard chow-fed rats. A similar up-regulation in mRNA expression was observed after offering sugar solutions. In conclusion, PLRP2 mRNA is expressed in the rat hypothalamus and both procolipase and PLRP-2 mRNA are down- regulated during fasting and up-regulated during conditions of metabolic excess, suggesting an involvement in signaling energy availability. © 2007 Elsevier B.V. All rights reserved. Keywords: Colipase PLRP2 Hypothalamus Fasting High-fat diet Sugar solutions 1. Introduction Pancreatic colipase is a required co-factor for pancreatic lipase, being necessary for the maintenance of pancreatic lipase acti- vity during hydrolysis of dietary triglycerides in the presence of bile salts (Borgström and Erlanson, 1971). In the intestine, colipase is cleaved from its precursor molecule, procolipase, through the action of trypsin (Borgström, 1984). This cleavage yields a peptide called enterostatin, being produced in equi- molar proportions to colipase (Erlanson-Albertsson, 1992; Mei et al., 1993). Enterostatin (APGPR) is a 5 amino acid long peptide that has been reported to inhibit the intake of a high-fat diet (Erlanson-Albertsson et al., 1991; Okada et al., 1993a). As ente- rostatin and colipase originate from the same precursor mole- cule, colipase mRNA can serve as a marker for enterostatin. Apart from being produced in the pancreas, procolipase has BRAIN RESEARCH 1185 (2007) 152 – 157 ⁎ Corresponding author. Fax: +46 46 222 45 46. E-mail address: andreas.lindqvist@med.lu.se (A. Lindqvist). 0006-8993/$ – see front matter © 2007 Elsevier B.V. All rights reserved. doi:10.1016/j.brainres.2007.09.022 available at www.sciencedirect.com www.elsevier.com/locate/brainres