Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002895 (sickle cell disease)
 11,747 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Polyunsaturated (PUFA) long-chain fatty acids (LCFAs) are more potent in eliciting molecular and tissue functional changes in monogastrics than saturated LCFA. From -21 through 10 days relative to parturition dairy cows were fed no supplemental LCFA (control), saturated LCFA (SFAT; mainly 16:0 and 18:0), or fish oil (FISH; high-PUFA). Twenty-seven genes were measured via quantitative RT-PCR in liver tissue on day -14 and day 10. Expression of nuclear receptor co-activators (CARM1, MED1), LCFA metabolism (ACSL1, SCD, ACOX1), and inflammation (IL6, TBK1, IKBKE) genes was lower with SFAT than control on day -14. Expression of SCD, however, was markedly lower with FISH than control or SFAT on both -14 and 10 days. FISH led to further decreases in expression on day 10 of LCFA metabolism (CD36, PLIN2, ACSL1, ACOX1), intracellular energy (UCP2, STK11, PRKAA1), de novo cholesterol synthesis (SREBF2), inflammation (IL6, TBK1, IKBKE), and nuclear receptor signaling genes (PPARD, MED1, NRIP1). No change in expression was observed for PPARA and RXRA. The increase of DGAT2, PLIN2, ACSL1, and ACOX1 on day 10 versus -14 in cows fed SFAT suggested upregulation of both beta-oxidation and lipid droplet (LD) formation. However, liver triacylglycerol concentration was similar among treatments. The hepatokine FGF21 and the gluconeogenic genes PC and PCK1 increased markedly on day 10 versus -14 only in controls. At the levels supplemented, the change in the profile of metabolic genes after parturition in cows fed saturated fat suggested a greater capacity for uptake of fatty acids and intracellular handling without excessive storage of LD.
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PMID:Dietary Lipid During Late-Pregnancy and Early-Lactation to Manipulate Metabolic and Inflammatory Gene Network Expression in Dairy Cattle Liver with a Focus on PPARs. 2382 24

In rodents, peroxisome proliferator-activated receptor delta (PPARD) is associated primarily with catabolism of fatty acids. However, the role of PPARD in regulating lipid metabolism in ruminant mammary gland remains unknown. In the present study, we assessed the mRNA abundance of PPARD at 3 stages of lactation in goat mammary tissue. Results revealed that PPARD had lower expression at peak lactation than in the nonlactating period. Luciferase assays revealed that GW0742 (GW), a specific PPARD ligand, enhanced the activity of the PPARD response element in goat mammary epithelial cells. Activation of PPARD by GW selectively upregulated the expression of genes related to fatty acid activation (ACSL1), lipid droplet formation (PLIN2), and transport (FABP4), and had no effect on genes involved in de novo fatty acid synthesis (ACACA and FASN), desaturation (SCD), hydrolysis and oxidation (PNPLA2 and CPT1A), transport and uptake (FABP3 and CD36), or triacylglycerol synthesis (DGAT1 and AGPAT6) in goat mammary epithelial cells. In contrast, knockdown of PPARD using small interfering RNA dramatically decreased the expression of genes related to fatty acid activation (ACSL1) and lipid formation (PLIN2) and increased the expression of genes related to fatty acid transport (FABP3) and triacylglycerol synthesis (AGPAT6 and DGAT1). The expression of genes related to fatty acid synthesis (FASN), hydrolysis (PNPLA2), and fatty acid oxidation (CPT1A) was downregulated significantly only after knockdown of PPARD in cells incubated with GW. We observed no significant change in fatty acid profiles. However, the total cellular triacylglycerol increased after knockdown of PPARD in goat mammary epithelial cells plus GW. Collectively, these results highlight an important role for PPARD in the homeostasis of ruminant mammary cells by facilitating fatty acid activation and lipid droplet formation and secretion.
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PMID:Peroxisome proliferator-activated receptor delta facilitates lipid secretion and catabolism of fatty acids in dairy goat mammary epithelial cells. 2786 96