Transcriptional Characterization of Porcine Leptin and Leptin Receptor Genes

Abstract

The leptin (LEP) and its receptor (LEPR) regulate food intake and energy balance through hypothalamic signaling. However, the LEP-LEPR axis seems to be more complex and its expression regulation has not been well described. In pigs, LEP and LEPR genes have been widely studied due to their relevance. Previous studies reported significant effects of SNPs located in both genes on growth and fatness traits. The aim of this study was to determine the expression profiles of LEP and LEPR across hypothalamic, adipose, hepatic and muscle tissues in Iberian x Landrace backcrossed pigs and to analyze the effects of gene variants on transcript abundance. To our knowledge, non porcine LEPR isoforms have been described rather than LEPRb. A short porcine LEPR isoform (LEPRa), that encodes a protein lacking the intracellular residues responsible of signal transduction, has been identified for the first time. The LEPRb isoform was only quantifiable in hypothalamus while LEPRa appeared widely expressed across tissues, but at higher levels in liver, suggesting that both isoforms would develop different roles. The unique LEP transcript showed expression in backfat and muscle. The effects of gene variants on transcript expression revealed interesting results. The LEPRc.1987C>T polymorphism showed opposite effects on LEPRb and LEPRa hypothalamic expression. In addition, one out of the 16 polymorphisms identified in the LEPR promoter region revealed high differential expression in hepatic LEPRa. These results suggest a LEPR isoform-specific regulation at tissue level. Conversely, non-differential expression of LEP conditional on the analyzed polymorphisms could be detected, indicating that its regulation is likely affected by other mechanisms rather than gene sequence variants. The present study has allowed a transcriptional characterization of LEP and LEPR isoforms on a range of tissues. Their expression patterns seem to indicate that both molecules develop peripheral roles apart from their known hypothalamic signal transduction function.

Unraveling molecular mechanisms involved in the development of leptin resistance using the pig as a model

“…2010; Pérez‐Montarelo et al . 2013) or triggered by a negative feedback loop owing to leptin abundance (Scarpace et al . 2001; Wilsey & Scarpace 2004), could be detected when profiling the expression of LEPRb transcripts, whereas the other mechanisms would remain elusive when using gene expression‐based methodologies.…”

“…2012; Pérez‐Montarelo et al . 2012, 2013, 2015). Moreover, tissue‐specific and transcript‐specific differential expression was revealed in pigs for different LEPR isoforms, and the hypothalamic expression of LEPRb and LEPRa (short isoform) transcripts showed opposite effects when comparing genotypes for an SNP (rs1112637715, LEPR c.1987C>T) significantly associated with increased growth, fatness and saturated fatty acid content in adipose tissue, probably owing to increased feed intake (Pérez‐Montarelo et al .…”

Modulatory Effects of Breed, Feeding Status, and Diet on Adipogenic, Lipogenic, and Lipolytic Gene Expression in Growing Iberian and Duroc Pigs

“…Finally, it is known that a high level of leptin induces lipolysis at the adipose tissue level [ 34 ]; in our case, the leptin gene showed the highest upregulation in the Iberian pigs (2.85 times), but we did not find a greater lipolysis in the Iberian pigs. Leptin effects are dependent on the leptin receptor, and it is known that Iberian pigs show leptin resistance, related to the presence of polymorphisms in the LEPR gene that either reduce its expression or reduces its signaling ability [ 44 , 45 ]. Thus, the Iberian pigs would be resistant to leptin-induced lipolysis.…”

TRIENNIAL LACTATION SYMPOSIUM/BOLFA: Adipokines affect mammary growth and function in farm animals1,2

“…A total of 6 alternatively spliced Ob-R isoforms have been identified in rodents and humans and can be grouped into short (Ob-Ra, Ob-Rc, Ob-Rd, and Ob-Rf), long (Ob-Rb), and secreted (Ob-Re) isoforms. Long and short Ob-R isoforms were also identified in farm animals (Kawachi et al, 2007;Pérez-Montarelo et al, 2013). These receptors share identical extracellular and transmembrane domains but present different intracellular portions (Wylie, 2011).…”