title: Paternal high-fat diet consumption induces common changes in the transcriptomes of retroperitoneal adipose and pancreatic islet tissues in female rat offspring.
abstract: We previously showed that paternal high-fat diet (HFD) consumption programs β-cell dysfunction in female rat offspring, together with transcriptome alterations in islets. Here we investigated the retroperitoneal white adipose tissue (RpWAT) transcriptome using gene and pathway enrichment and pathway analysis to determine whether commonly affected network topologies exist between these two metabolically related tissues. In RpWAT, 5108 genes were differentially expressed due to a paternal HFD; the top 5 significantly enriched networks identified by pathway analysis in offspring of HFD fathers compared with those of fathers fed control diet were: mitochondrial and cellular response to stress, telomerase signaling, cell death and survival, cell cycle, cellular growth and proliferation, and cancer. A total of 187 adipose olfactory receptor genes were down-regulated. Interrogation against the islet transcriptome identified specific gene networks and pathways, including olfactory receptor genes that were similarly affected in both tissues (411 common genes, P<0.05). In particular, we highlight a common molecular network, cell cycle and cancer, with the same hub gene, Myc, suggesting early onset developmental changes that persist, shared responses to programmed systemic factors, or crosstalk between tissues. Thus, paternal HFD consumption triggers unique gene signatures, consistent with premature aging and chronic degenerative disorders, in both RpWAT and pancreatic islets of daughters.
authors.affiliation: 1Department of Pharmacology, School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia, 2052. m.morris@unsw.edu.au.
authors.forename: Sheau-Fang
authors.initials: SF
authors.lastname: Ng
authors.forename: Ruby C Y
authors.initials: RC
authors.lastname: Lin
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Maloney
authors.forename: Neil A
authors.initials: NA
authors.lastname: Youngson
authors.forename: Julie A
authors.initials: JA
authors.lastname: Owens
authors.forename: Margaret J
authors.initials: MJ
authors.lastname: Morris
mesh_terms: D000818:Animals; D016000:Cluster Analysis; D059305:Diet, High-Fat; D004041:Dietary Fats / Q000008:administration & dosage; D005260:Female; D053263:Gene Regulatory Networks / Q000187:drug effects / Q000235:genetics; D050152:Intra-Abdominal Fat / Q000378:metabolism*; D007515:Islets of Langerhans / Q000378:metabolism*; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D059467:Transcriptome / Q000187:drug effects / Q000235:genetics*
chemical_list: D004041:Dietary Fats
keywords: chronic degenerative disorder; developmental programming; obesity; olfactory receptor genes; premature aging