Abstract
To explore the large-scale effect of peroxisome proliferator-activated receptor γ (PPARG) in goat mammary epithelial cells (GMEC), an oligonucleotide microarray platform was used for transcriptome profiling in cells overexpressing PPARG and incubated with or without rosiglitazone (ROSI, a PPARγ agonist). A total of 1143 differentially expressed genes (DEG) due to treatment were detected. The Dynamic Impact Approach (DIA) analysis uncovered the most impacted and induced pathways “fatty acid elongation in mitochondria,” “glycosaminoglycan biosynthesis-keratan sulfate,” and “pentose phosphate pathway.” The data highlights the central role of PPARG in milk fatty acid metabolism via controlling fatty acid elongation, biosynthesis of unsaturated fatty acid, lipid formation, and lipid secretion; furthermore, its role related to carbohydrate metabolism promotes the production of intermediates required for milk fat synthesis. Analysis of upstream regulators indicated that PPARG participates in multiple physiological processes via controlling or cross talking with other key transcription factors such as PPARD and NR1H3 (also known as liver-X-receptor-α). This transcriptome-wide analysis represents the first attempt to better understand the biological relevance of PPARG expression in ruminant mammary cells. Overall, the data underscored the importance of PPARG in mammary lipid metabolism and transcription factor control.
Highlights
Ruminant milk products are common and popular throughout the world
When compared with cells expressing PPARG with and without ROSI, the analysis indicated that the number of upregulated and downregulated differentially expressed genes (DEG) was 221 and 483, respectively
Using cross-species hybridization microarray data, the present data support a role for PPARG activation on biological processes including and going beyond milk fat synthesis
Summary
Ruminant milk products are common and popular throughout the world. Milk fat is an important component of dairy products and is a major contributor to dietary energy density. The higher concentrations of unsaturated and medium-chain fatty acids are responsible for the characteristic “goaty” odour of goat milk and confer unique organoleptic properties [1]. Recent evidence indicates that milk fat biosynthesis is regulated by key transcription factors including peroxisome proliferator-activated receptor γ (PPARG) [2, 3]. It is well established that PPARG is a critical transcription factor controlling adipogenesis and glucose metabolism in various cells in nonruminants [4,5,6]. After binding of ligands (e.g., rosiglitazone (ROSI) or pioglitazone), PPARG causes conformational changes in the receptor [7, 8] and forms a heterodimeric complex with RXR proteins and binds to PPAR response element (PPRE) upstream of target genes [9]. Through controlling the downstream genes, PPARG regulates adipocyte differentiation and promotes insulin sensitivity in human and rodents [7].
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