Molecular recognition of long chain fatty acids by peroxisome proliferator-activated receptor α

2008 ◽  
Vol 18 (1) ◽  
pp. 8-19 ◽  
Author(s):  
Osman A. B. S. M. Gani ◽  
Ingebrigt Sylte
Keyword(s):  
Fatty Acids ◽  
Molecular Recognition ◽  
Peroxisome Proliferator ◽  
Long Chain Fatty Acids ◽  
Peroxisome Proliferator Activated Receptor ◽  
Long Chain ◽  
Chain Fatty Acids

Very long-chain-fatty acids enhance adipogenesis through coregulation of Elovl3 and PPARγ in 3T3-L1 cells

2012 ◽  
Vol 302 (12) ◽  
pp. E1461-E1471 ◽  
Author(s):  
Takeshi Kobayashi ◽  
Ko Fujimori
Keyword(s):  
Fatty Acids ◽  
Target Genes ◽  
Mrna Level ◽  
Peroxisome Proliferator ◽  
Long Chain Fatty Acids ◽  
Peroxisome Proliferator Activated Receptor ◽  
Lipogenic Genes ◽  
Pparγ Agonist ◽  
Long Chain ◽  
Chain Fatty Acids

Here, we show that Elovl3 (elongation of very long-chain fatty acids 3) was involved in the regulation of the progression of adipogenesis through activation of peroxisome proliferator-activated receptor (PPAR)γ in mouse adipocytic 3T3-L1 cells. The expression of the Elovl3 gene increased during adipogenesis, the expression pattern of which was similar to that of the PPARγ gene. Troglitazone, a PPARγ agonist, enhanced Elovl3 expression in adipocytes, as it did that of other PPARγ target genes. Promoter-reporter analysis demonstrated that three PPAR-responsive elements in the Elovl3 gene promoter had the potential to activate its expression in 3T3-L1 cells. Moreover, a chromatin immunoprecipitation assay revealed that PPARγ bound these PPAR-responsive elements of the Elovl3 promoter. When the Elovl3 mRNA level was suppressed by its siRNAs, the level of intracellular triglycerides was significantly decreased, and the expression levels of adipogenic, lipolytic, and lipogenic genes were also repressed. In a mammalian two-hybrid assay, C18:1 and C20:1 very long-chain fatty acids (VLCFAs), which are the products of Elovl3 and activated PPARγ function. In addition, these same VLCFAs could prevent the Elovl3 siRNA-mediated suppression of adipogenesis by enhancing the expression of adipogenic, lipolytic, and lipogenic genes in adipocytes. Moreover, this VLCFAs-mediated activation was repressed by a PPARγ antagonist. These results indicate that the expression of the Elovl3 gene was activated by PPARγ during adipogenesis. Elovl3-produced C18:1 and C20:1 VLCFAs acted as agonists of PPARγ in 3T3-L1 cells. Thus, the Elovl3-PPARγ cascade is a novel regulatory circuit for the regulation of adipogenesis through improvement of PPARγ function in adipocytes.

scholarly journals Peroxisome-proliferator-activated receptor δ mediates the effects of long-chain fatty acids on post-confluent cell proliferation

2000 ◽  
Vol 350 (1) ◽  
pp. 93-98 ◽  
Author(s):  
Chantal JEHL-PIETRI ◽  
Claire BASTIE ◽  
Isabelle GILLOT ◽  
Serge LUQUET ◽  
Paul A. GRIMALDI
Keyword(s):  
Fatty Acids ◽  
Cell Proliferation ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
Ectopic Expression ◽  
Peroxisome Proliferator ◽  
Long Chain Fatty Acids ◽  
Control Of Gene Expression ◽  
Long Chain ◽  
Chain Fatty Acids

Nutritional long-chain fatty acids control adipose tissue mass by regulating the number and the size of adipocytes. It is now established that peroxisome-proliferator-activated receptors (PPARs) play crucial functions in the control of gene expression and the level of cell differentiation. PPARγ, which is activated by specific prostanoids, is a key factor in activating terminal differentiation and adipogenesis. We have recently demonstrated that PPARδ, once activated by fatty acids, drives the expression of a limited set of genes, including that encoding PPARγ, thereby inducing adipose differentiation. Thus far, the mechanism of action of fatty acids in the control of preadipocyte proliferation has remained unknown. We show here that PPARδ is directly implicated in fatty acid-induced cell proliferation. Ectopic expression of PPARδ renders 3T3C2 cells capable of responding to treatment with long-chain fatty acids by a resumption of mitosis, and this effect is limited to a few days after confluence. This response is restricted to PPARδ activators and, for fatty acids, takes place within the range of concentrations found to trigger differentiation of preadipocytes both in vitro and in vivo. Furthermore, the use of a mutated inactive PPARδ demonstrated that transcriptional activity of the nuclear receptor is required to mediate fatty acid-induced proliferation. These data demonstrate that PPARδ, as a transcription factor, is directly implicated in fatty acid-induced proliferation, and this could explain the hyperplastic development of adipose tissue that occurs in high-fat-fed animals.

scholarly journals Hepatic Peroxisomal Fatty Acid β-Oxidation Is Regulated by Liver X Receptor α

Endocrinology ◽  
2005 ◽  
Vol 146 (12) ◽  
pp. 5380-5387 ◽  
Author(s):  
Tonghuan Hu ◽  
Patricia Foxworthy ◽  
Angela Siesky ◽  
James V. Ficorilli ◽  
Hong Gao ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Liver Steatosis ◽  
Liver X Receptor ◽  
Acid Oxidation ◽  
Peroxisome Proliferator ◽  
Long Chain Fatty Acids ◽  
Lxr Agonists ◽  
Long Chain ◽  
Chain Fatty Acids

Peroxisomes are the exclusive site for the β-oxidation of very-long-chain fatty acids of more than 20 carbons in length (VLCFAs). Although the bulk of dietary long-chain fatty acids are oxidized in the mitochondria, VLCFAs cannot be catabolized in mitochondria and must be shortened first by peroxisomal β-oxidation. The regulation of peroxisomal, mitochondrial, and microsomal fatty acid oxidation systems in liver is mediated principally by peroxisome proliferator-activated receptor α (PPARα). In this study we provide evidence that the liver X receptor (LXR) regulates the expression of the genetic program for peroxisomal β-oxidation in liver. The genes encoding the three enzymes of the classic peroxisomal β-oxidation cycle, acyl-coenzyme A (acyl-CoA) oxidase, enoyl-CoA hydratase/L-3-hydroxyacyl-CoA dehydrogenase, and 3-ketoacyl-CoA thiolase, are activated by the LXR ligand, T0901317. Accordingly, administration of T0901317 in mice promoted a dose-dependent and greater than 2-fold increase in the rate of peroxisomal β-oxidation in the liver. The LXR effect is independent of PPARα, because T0901317-induced peroxisomal β-oxidation in the liver of PPARα-null mice. Interestingly, T0901317-induced peroxisomal β-oxidation is dependent on the LXRα isoform, but not the LXRβ isoform. We propose that induction of peroxisomal β-oxidation by LXR agonists may serve as a counterregulatory mechanism for responding to the hypertriglyceridemia and liver steatosis that is promoted by potent LXR agonists in vivo; however, additional studies are warranted.

scholarly journals Differential Effects of Fatty Acid Saturation and Chain Length on NASH in Juvenile Iberian Pigs

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 682-682 ◽  
Author(s):  
Kayla Dillard ◽  
Morgan Coffin ◽  
Gabriella Hernandez ◽  
Victoria Smith ◽  
Catherine Johnson ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Body Weight ◽  
Fatty Acid ◽  
Liver Injury ◽  
Olive Oil ◽  
Coconut Oil ◽  
Long Chain Fatty Acids ◽  
Medium Chain ◽  
Long Chain ◽  
Chain Fatty Acids

Abstract Objectives Non-alcoholic fatty liver disease (NAFLD) represents the major cause of pediatric chronic liver pathology in the United States. The objective of this study was to compare the relative effect of inclusion of isocaloric amounts of saturated medium-chain fatty acids (hydrogenated coconut oil), saturated long-chain fatty acids (lard) and unsaturated long-chain fatty acids (olive oil) on endpoints of NAFLD and insulin resistance. Methods Thirty-eight 15-d-old Iberian pigs were fed 1 of 4 diets containing (g/kg body weight × d) 1) control (CON; n = 8): 0 g fructose, 10.5 g fat, and 187 kcal metabolizable energy (ME), 2) lard (LAR; n = 10): 21.6 g fructose, 17.1 g fat (100% lard) and 299 kcal ME, 3) hydrogenated coconut oil (COCO; n = 10): 21.6 g fructose, 16.9 g fat (42.5% lard and 57.5% coconut oil) and 299 kcal ME, and 4) olive oil (OLV, n = 10): 21.6 g fructose, 17.1 g fat (43.5% lard and 56.5% olive oil) and 299 kcal ME, for 9 consecutive weeks. Body weight was recorded every 3 d. Serum markers of liver injury and dyslipidemia were measured on d 60 at 2 h post feeding, with all other serum measures assessed on d 70. Liver tissue was collected on d 70 for histology, triacylglyceride (TG) quantification, and metabolomics analysis. Results Tissue histology indicated the presence of steatosis in LAR, COCO and OLV compared with CON (P ≤ 0.001), with a further increase in in non-alcoholic steatohepatitis (NASH) in OLV and COCO compared with LAR (P ≤ 0.01). Alanine and aspartate aminotransferases were higher in COCO and OLV (P ≤ 0.01) than CON. All treatment groups had lower liver concentrations of methyl donor's choline and betaine versus CON, while bile acids were differentially changed (P ≤ 0.05). COCO had higher levels of TGs with less carbons (Total carbons < 52) than all other groups (P ≤ 0.05). Several long-chain acylcarnitines involved in fat oxidation were higher in OLV versus all other groups (P ≤ 0.05). Conclusions Inclusion of fats enriched in medium-chain saturated and long-chain unsaturated fatty acids in a high-fructose high-fat diet increased liver injury, compared with fats with a long-chain saturated fatty acid profile. Further research is required to investigate the mechanisms causing this difference in physiological response to these dietary fat sources. Funding Sources ARI, AcornSeekers.

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