title: Peroxisome proliferator-activated receptor γ1 and γ2 isoforms alter lipogenic gene networks in goat mammary epithelial cells to different extents.
abstract: In nonruminants, the alternative splicing of peroxisome proliferator-activated receptor γ (PPARG) generates PPARG1 and PPARG2 isoforms. Although transcriptional control differences between isoforms have been reported in human adipose tissue, their roles in ruminant mammary cells are not well known. To assess which of these isoforms is more closely associated with the regulation of mammary lipogenic pathways, their tissue distribution was analyzed and the expression of key genes regulating lipogenic gene networks was measured after overexpression of the 2 isoforms in goat mammary epithelial cells (GMEC). The expression of PPARG2 was markedly greater in adipose tissue, whereas PPARG1 is the main isoform in goat mammary tissue (ratio of PPARG1:PPARG2 was close to 37:1). As was reported in previous work, PPARG1 upregulated the transcription regulators SREBF1 and PPARG and the lipogenic genes FASN, ACACA, and SCD. Along with a tendency for greater expression of AGPAT6, DGAT1, and PLIN2, these data suggest that PPARG1 is the isoform controlling lipogenesis in mammary cells. Addition of the PPARG ligand rosiglitazone (ROSI) to GMEC overexpressing both isoforms upregulated the expression of LPL and CD36, which help control uptake of long-chain fatty acids into mammary cells. Other responses to ROSI addition to GMEC overexpressing PPARG1 and PPARG2 included upregulation of AGPAT6, DGAT1, INSIG1, SREBF1, and NR1H3. Although the data suggest that both PPARG1 and PPARG2 could affect mammary lipogenesis via control of gene expression when stimulated (e.g., by ROSI), the fact that PPARG1 is more abundant in mammary tissue and that its overexpression alone upregulated key lipogenic gene networks suggest that it is the more important isoform in goat mammary cells.
authors.affiliation: Shaanxi Key Laboratory of Molecular Biology for Agriculture, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, China.
authors.forename: H B
authors.initials: HB
authors.lastname: Shi
authors.affiliation: Shaanxi Key Laboratory of Molecular Biology for Agriculture, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, China; Mammalian NutriPhysioGenomics, Department of Animal Sciences and Division of Nutritional Sciences, University of Illinois, Urbana 61801.
authors.forename: W S
authors.initials: WS
authors.lastname: Zhao
authors.affiliation: Shaanxi Key Laboratory of Molecular Biology for Agriculture, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, China. Electronic address: luojun@nwsuaf.edu.cn.
authors.forename: J
authors.initials: J
authors.lastname: Luo
authors.affiliation: Shaanxi Key Laboratory of Molecular Biology for Agriculture, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, China.
authors.forename: D W
authors.initials: DW
authors.lastname: Yao
authors.affiliation: Shaanxi Key Laboratory of Molecular Biology for Agriculture, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, China.
authors.forename: Y T
authors.initials: YT
authors.lastname: Sun
authors.affiliation: Shaanxi Key Laboratory of Molecular Biology for Agriculture, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, China.
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.affiliation: Shaanxi Key Laboratory of Molecular Biology for Agriculture, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, China.
authors.forename: H P
authors.initials: HP
authors.lastname: Shi
authors.affiliation: Mammalian NutriPhysioGenomics, Department of Animal Sciences and Division of Nutritional Sciences, University of Illinois, Urbana 61801. Electronic address: jloor@illinois.edu.
authors.forename: J J
authors.initials: JJ
authors.lastname: Loor
mesh_terms: D000103:Acetyl-CoA Carboxylase / Q000235:genetics / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism; D051048:Diacylglycerol O-Acyltransferase / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D054890:Fatty Acid Synthase, Type I / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D005992:Glycerol-3-Phosphate O-Acyltransferase / Q000235:genetics / Q000378:metabolism; D006041:Goats; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D050155:Lipogenesis / Q000235:genetics; D008071:Lipoprotein Lipase / Q000235:genetics / Q000378:metabolism; D008321:Mammary Glands, Animal / Q000166:cytology* / Q000378:metabolism; D047495:PPAR gamma / Q000235:genetics* / Q000378:metabolism; D020033:Protein Isoforms; D000077154:Rosiglitazone; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000009:adverse effects; D015854:Up-Regulation
chemical_list: D018955:CD36 Antigens; D047908:Intracellular Signaling Peptides and Proteins; D047495:PPAR gamma; D020033:Protein Isoforms; D051780:Sterol Regulatory Element Binding Protein 1; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D005992:Glycerol-3-Phosphate O-Acyltransferase; D051048:Diacylglycerol O-Acyltransferase; D054890:Fatty Acid Synthase, Type I; D008071:Lipoprotein Lipase; D000103:Acetyl-CoA Carboxylase
keywords: fatty acid metabolism; gene network; lactation; mammary gland; nuclear receptor