Hypothalamic Transcriptome Analysis Reveals Male-specific Differences in Molecular Pathways Related to Oxidative Phosphorylation Between Iberian Pig Genotypes

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2022 Aug 16

PMID 35972914

Authors

Ana Heras-Molina

Yolanda Nunez

Rita Benitez

Jose Luis Pesantez-Pacheco

Consolacion Garcia-Contreras

Marta Vazquez-Gomez

Susana Astiz

Beatriz Isabel

Antonio Gonzalez-Bulnes

Cristina Ovilo

Affiliations

Soon will be listed here.

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.

References

Tsikas D . Assessment of lipid peroxidation by measuring malondialdehyde (MDA) and relatives in biological samples: Analytical and biological challenges. Anal Biochem. 2016; 524:13-30. DOI: 10.1016/j.ab.2016.10.021. View

Schagger H, Pfeiffer K . Supercomplexes in the respiratory chains of yeast and mammalian mitochondria. EMBO J. 2000; 19(8):1777-83. PMC: 302020. DOI: 10.1093/emboj/19.8.1777. View

Kondas K, Szlama G, Trexler M, Patthy L . Both WFIKKN1 and WFIKKN2 have high affinity for growth and differentiation factors 8 and 11. J Biol Chem. 2008; 283(35):23677-84. PMC: 3259755. DOI: 10.1074/jbc.M803025200. View

Akira S, Nishio Y, Inoue M, Wang X, Wei S, Matsusaka T . Molecular cloning of APRF, a novel IFN-stimulated gene factor 3 p91-related transcription factor involved in the gp130-mediated signaling pathway. Cell. 1994; 77(1):63-71. DOI: 10.1016/0092-8674(94)90235-6. View

Tan S, Zhou Y, Zhao H, Wu J, Yu H, Yang Y . Comprehensive transcriptome analysis of hypothalamus reveals genes associated with disorders of sex development in pigs. J Steroid Biochem Mol Biol. 2021; 210:105875. DOI: 10.1016/j.jsbmb.2021.105875. View

Anders S, Pyl P, Huber W . HTSeq--a Python framework to work with high-throughput sequencing data. Bioinformatics. 2014; 31(2):166-9. PMC: 4287950. DOI: 10.1093/bioinformatics/btu638. View

Benitez R, Trakooljul N, Nunez Y, Isabel B, Murani E, de Mercado E . Breed, Diet, and Interaction Effects on Adipose Tissue Transcriptome in Iberian and Duroc Pigs Fed Different Energy Sources. Genes (Basel). 2019; 10(8). PMC: 6723240. DOI: 10.3390/genes10080589. View

Misu H, Takamura T, Matsuzawa N, Shimizu A, Ota T, Sakurai M . Genes involved in oxidative phosphorylation are coordinately upregulated with fasting hyperglycaemia in livers of patients with type 2 diabetes. Diabetologia. 2006; 50(2):268-77. DOI: 10.1007/s00125-006-0489-8. View

Hirschey M, Shimazu T, Goetzman E, Jing E, Schwer B, Lombard D . SIRT3 regulates mitochondrial fatty-acid oxidation by reversible enzyme deacetylation. Nature. 2010; 464(7285):121-5. PMC: 2841477. DOI: 10.1038/nature08778. View

10.

Lopez-Bote C . Sustained utilization of the Iberian pig breed. Meat Sci. 2011; 49S1:S17-27. View

11.

Cirera S, Jensen M, Elbrond V, Moesgaard S, Christoffersen B, Kadarmideen H . Expression studies of six human obesity-related genes in seven tissues from divergent pig breeds. Anim Genet. 2013; 45(1):59-66. DOI: 10.1111/age.12082. View

12.

Jonckheere A, Smeitink J, Rodenburg R . Mitochondrial ATP synthase: architecture, function and pathology. J Inherit Metab Dis. 2011; 35(2):211-25. PMC: 3278611. DOI: 10.1007/s10545-011-9382-9. View

13.

Dahlman I, Forsgren M, Sjogren A, Nordstrom E, Kaaman M, Naslund E . Downregulation of electron transport chain genes in visceral adipose tissue in type 2 diabetes independent of obesity and possibly involving tumor necrosis factor-alpha. Diabetes. 2006; 55(6):1792-9. DOI: 10.2337/db05-1421. View

14.

Torres-Rovira L, Gonzalez-Anover P, Astiz S, Caro A, Lopez-Bote C, Ovilo C . Effect of an obesogenic diet during the juvenile period on growth pattern, fatness and metabolic, cardiovascular and reproductive features of Swine with obesity/leptin resistance. Endocr Metab Immune Disord Drug Targets. 2012; 13(2):143-51. DOI: 10.2174/1871530311313020002. View

15.

Rogge M . The role of impaired mitochondrial lipid oxidation in obesity. Biol Res Nurs. 2009; 10(4):356-73. DOI: 10.1177/1099800408329408. View

16.

Beach T, Adler C, Sue L, Serrano G, Shill H, Walker D . Arizona Study of Aging and Neurodegenerative Disorders and Brain and Body Donation Program. Neuropathology. 2015; 35(4):354-89. PMC: 4593391. DOI: 10.1111/neup.12189. View

17.

Garcia-Contreras C, Madsen O, Groenen M, Lopez-Garcia A, Vazquez-Gomez M, Astiz S . Impact of genotype, body weight and sex on the prenatal muscle transcriptome of Iberian pigs. PLoS One. 2020; 15(1):e0227861. PMC: 6986718. DOI: 10.1371/journal.pone.0227861. View

18.

Iwata S, Lee J, Okada K, Lee J, Iwata M, Rasmussen B . Complete structure of the 11-subunit bovine mitochondrial cytochrome bc1 complex. Science. 1998; 281(5373):64-71. DOI: 10.1126/science.281.5373.64. View

19.

Yoshikawa S, Muramoto K, Shinzawa-Itoh K, Aoyama H, Tsukihara T, Shimokata K . Proton pumping mechanism of bovine heart cytochrome c oxidase. Biochim Biophys Acta. 2006; 1757(9-10):1110-6. DOI: 10.1016/j.bbabio.2006.06.004. View

20.

Jacob R, Mudd A, Alexander L, Lai C, Dilger R . Comparison of Brain Development in Sow-Reared and Artificially Reared Piglets. Front Pediatr. 2016; 4:95. PMC: 5018487. DOI: 10.3389/fped.2016.00095. View