Hypothalamic transcriptome analysis reveals male-specific differences in molecular pathways related to oxidative phosphorylation between Iberian pig genotypes

Abstract

The hypothalamus is implicated in controlling feeding and adiposity, besides many other physiological functions, and thus can be of great importance in explaining productive differences between lean and fatty pig breeds. The present study aimed to evaluate the hypothalamic transcriptome of pure Iberian (IBxIB) and Large White x Iberian crossbreds (IBxLW) at 60 days-old, produced in a single maternal environment. Results showed the implication of gender and genotype in the hypothalamic transcriptome, with 51 differentially expressed genes (DEGs) between genotypes and 10 DEGs between genders. Fourteen genotype by sex interactions were found, due to a higher genotype effect on transcriptome found in males. In fact, just 31 DEGs were identified when using only females but 158 using only males. A higher expression of genes related to mitochondrial activity in IBxIB male animals (ND3, ND4, ND5, UQCRC2 and ATP6) was found, which was related to a higher oxidative phosphorylation and greater reactive oxygen species and nitric oxide production. IBxLW male animals showed higher expression of SIRT3 regulator, also related to mitochondrial function. When females were analysed, such differences were not found, since only some differences in genes related to the tricarboxylic acid cycle. Thus, the results indicate a significant effect and interaction of the breed and the sex on the hypothalamic transcriptome at this early age.

Fig 1. Clustering of mitochondrial DEGs related to electron transport and oxydative phosphorilation obtained with the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) software.

Line thickness indicates the strenght of data suport.

Fig 2. Oxidative phosphorylation pathway with genes predicted to be activated in pure Iberian (IBxIB; coloured in green) males when compared with Iberian x Large White crossbreds (IBxLW; coloured in red), obtained using Ingenuity Pathway Software (IPA).

Fig 3. Causal network predicted for STAT3 regulator showing its relationship with obesity and inflammatory response, obtained using Ingenuity Pathway Analysis (IPA).

IBxIB = pure Iberian pigs; IBxLW = Iberian x Large White crossbreds.

Fig 4. Venn diagram of the analyses of the genotype effect performed in the present study.

Genotype: Hypothalamic transcriptome analysis of all IBxIB vs. all IBxLW 60 days-old pigs; Genotype females: Hypothalamic transcriptome analysis of IBxIB vs. IBxLW 60 days-old females; Genotype males: Hypothalamic transcriptome analysis of IBxIB vs. IBxLW 60 days-old males; Interaction: Hypothalamic transcriptome analysis of the genotype by sex interaction in 60 days-old pigs. IBxIB = pure Iberian pigs; IBxLW = Iberian x Large White crossbreds.