scholarly journals Fine metabolic regulation in ruminants via nutrient–gene interactions: saturated long-chain fatty acids increase expression of genes involved in lipid metabolism and immune response partly through PPAR-α activation

2011 ◽  
Vol 107 (2) ◽  
pp. 179-191 ◽  
Author(s):  
Massimo Bionaz ◽  
Betsy J. Thering ◽  
Juan J. Loor
Keyword(s):  
Fatty Acids ◽  
Lipid Metabolism ◽  
Metabolic Regulation ◽  
Target Genes ◽  
Long Chain Fatty Acids ◽  
Response Data ◽  
Expression Of Genes ◽  
Gene Network Analysis ◽  
Long Chain ◽  
Chain Fatty Acids

Madin–Darby Bovine Kidney cells cultured with 150 μm of Wy-14 643 (WY, PPARα agonist) or twelve long-chain fatty acids (LCFA; 16 : 0, 18 : 0, cis-9–18 : 1, trans-10–18 : 1, trans-11–18 : 1, 18 : 2n-6, 18 : 3n-3, cis-9, trans-11–18 : 2, trans-10, cis-12–18 : 2, 20 : 0, 20 : 5n-3 and 22 : 6n-3) were used to uncover PPAR-α target genes and determine the effects of LCFA on expression of thirty genes with key functions in lipid metabolism and inflammation. Among fifteen known PPAR-α targets in non-ruminants, ten had greater expression with WY, suggesting that they are bovine PPAR-α targets. The expression of SPP1 and LPIN3 was increased by WY, with no evidence of a similar effect in the published literature, suggesting that both represent bovine-specific PPAR-α targets. We observed the strongest effect on the expression of PPAR-α targets with 16 : 0, 18 : 0 and 20 : 5n-3.When considering the overall effect on expression of the thirty selected genes 20 : 5n-3, 16 : 0 and 18 : 0 had the greatest effect followed by 20 : 0 and c9t11–18 : 2. Gene network analysis indicated an overall increase in lipid metabolism by WY and all LCFA with a central role of PPAR-α but also additional putative transcription factors. A greater increase in the expression of inflammatory genes was observed with 16 : 0 and 18 : 0. Among LCFA, 20 : 5n-3, 16 : 0 and 18 : 0 were the most potent PPAR-α agonists. They also affected the expression of non-PPAR-α targets, eliciting an overall increase in the expression of genes related to lipid metabolism, signalling and inflammatory response. Data appear to highlight a teleological evolutionary adaptation of PPAR in ruminants to cope with the greater availability of saturated rather than unsaturated LCFA.

Effects of cold acclimation on lipid metabolism in adipose tissue

1961 ◽  
Vol 200 (4) ◽  
pp. 847-850 ◽  
Author(s):  
Judith K. Patkin ◽  
E. J. Masoro
Keyword(s):  
Fatty Acids ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
Lipid Metabolism ◽  
Cold Acclimation ◽  
Long Chain Fatty Acids ◽  
Synthetic Capacity ◽  
And Control ◽  
Long Chain ◽  
Chain Fatty Acids

Cold acclimation is known to alter hepatic lipid metabolism. Liver slices from cold-acclimated rats have a greatly depressed capacity to synthesize long-chain fatty acids from acctate-1-C14. Since adipose tissue is the major site of lipogenic activity in the intact animal, its fatty acid synthetic capacity was studied. In contrast to the liver, it was found that adipose tissue from the cold-acclimated rat synthesized three to six times as much long-chain fatty acids per milligram of tissue protein as the adipose tissue from the control rat living at 25°C. Evidence is presented indicating that adipose tissue from cold-acclimated and control rats esterify long-chain fatty acids at the same rate. The ability of adipose tissue to oxidize palmitic acid to CO2 was found to be unaltered by cold acclimation. The fate of the large amount of fatty acid synthesized in the adipose tissue of cold-acclimated rats is discussed.

scholarly journals Accumulation of long-chain fatty acids in the tumor microenvironment drives dysfunction in intrapancreatic CD8+ T cells

2020 ◽  
Vol 217 (8) ◽  
Author(s):  
Teresa Manzo ◽  
Boone M. Prentice ◽  
Kristin G. Anderson ◽  
Ayush Raman ◽  
Aislyn Schalck ◽  
...  
Keyword(s):  
Fatty Acids ◽  
T Cells ◽  
Lipid Metabolism ◽  
Tumor Microenvironment ◽  
Cd8 T Cells ◽  
Metabolic Reprogramming ◽  
Long Chain Fatty Acids ◽  
Cell Functions ◽  
Long Chain ◽  
Chain Fatty Acids

CD8+ T cells are master effectors of antitumor immunity, and their presence at tumor sites correlates with favorable outcomes. However, metabolic constraints imposed by the tumor microenvironment (TME) can dampen their ability to control tumor progression. We describe lipid accumulation in the TME areas of pancreatic ductal adenocarcinoma (PDA) populated by CD8+ T cells infiltrating both murine and human tumors. In this lipid-rich but otherwise nutrient-poor TME, access to using lipid metabolism becomes particularly valuable for sustaining cell functions. Here, we found that intrapancreatic CD8+ T cells progressively accumulate specific long-chain fatty acids (LCFAs), which, rather than provide a fuel source, impair their mitochondrial function and trigger major transcriptional reprogramming of pathways involved in lipid metabolism, with the subsequent reduction of fatty acid catabolism. In particular, intrapancreatic CD8+ T cells specifically exhibit down-regulation of the very-long-chain acyl-CoA dehydrogenase (VLCAD) enzyme, which exacerbates accumulation of LCFAs and very-long-chain fatty acids (VLCFAs) that mediate lipotoxicity. Metabolic reprogramming of tumor-specific T cells through enforced expression of ACADVL enabled enhanced intratumoral T cell survival and persistence in an engineered mouse model of PDA, overcoming one of the major hurdles to immunotherapy for PDA.

Long-chain fatty acids differentially alter lipogenesis in bovine and caprine mammary slices

2012 ◽  
Vol 80 (1) ◽  
pp. 89-95 ◽  
Author(s):  
Laurence Bernard ◽  
Mohamad B. Montazer Torbati ◽  
Benoit Graulet ◽  
Christine Leroux ◽  
Yves Chilliard
Keyword(s):  
Fatty Acids ◽  
Mammary Tissue ◽  
Mrna Levels ◽  
Long Chain Fatty Acids ◽  
Expression Of Genes ◽  
Cultured Slices ◽  
Long Chain ◽  
Chain Fatty Acids ◽  
Mammary Tissues

Indirect comparisons from studies in vivo have suggested that caprine mammary tissue is less sensitive than bovine mammary tissue to the anti-lipogenic effect of long-chain fatty acids (LCFA), including specific rumen biohydrogenation (RBH) intermediates of polyunsaturated fatty acids (PUFA). Our objective was to investigate the effects on lipogenesis of 18-carbon LCFA differing in the degree of unsaturation and/or double bond conformation using cultured slices of bovine and caprine mammary tissues. Mammary tissues were collected from five multiparous Holstein × Normande cows and six multiparous Alpine goats in mid lactation. The expression of genes involved in milk component synthesis was measured in tissues collected at slaughter and after slice preparation:FASN, SCD1, CD36, SREBF1andPPARG1mRNA levels were higher in bovine than caprine samples, whereas the opposite was observed forCSN2mRNA levels. Bovine and caprine mammary slices were incubated for 20 h in a medium with BSA (control), cis-9-18 : 1, 18 : 2n-6, 18 : 3n-3, cis-9, trans-11-CLA, or trans-10, cis-12-CLA (the latter at 3 increasing concentrations: C1 (0·11 mm), C2 (0·16 mm), C3 (0·37 mm)). Lipogenesis was estimated by measuring the incorporation of14C-acetate into total lipid. Significant differences of individual LCFA (P < 0·05) were observed between species: bovine tissue showed a decrease in total lipogenesis with 18 : 2n-6, 18 : 3n-3, trans-10,cis-12-CLA (C2 and C3) while caprine tissue showed an increase after treatment with 18 : 3n-3, cis-9, trans-11-CLA or trans-10, cis-12-CLA (C3). These results were not related to the mRNA abundance of our set of genes in the mammary slices after incubation. In conclusion, this study demonstrates that caprine mammary slices reacted differently from bovine mammary slices to the anti-lipogenic activity of specific LCFA and suggests that regulation of lipogenesis via other genes and/or at protein level and enzyme activity may be involved.

scholarly journals Effect of unsaturated C18 fatty acids (oleic, linoleic and α-linolenic acids) on ruminal fermentation and production of fatty acids isomers in artificial rumen

2008 ◽  
Vol 52 (No. 3) ◽  
pp. 87-94 ◽  
Author(s):  
D. Jalc ◽  
M. Certik ◽  
K. Kundrikova ◽  
P. Namestkova
Keyword(s):  
Fatty Acids ◽  
Lipid Metabolism ◽  
Rumen Fluid ◽  
Rumen Fermentation ◽  
Long Chain Fatty Acids ◽  
Ruminal Fermentation ◽  
Trans Isomers ◽  
Stabilization Period ◽  
Long Chain ◽  
Chain Fatty Acids

The objective of this study was to examine the effect of oleic (OA), linoleic (LA) and &alpha;-linolenic (ALA) acid used as supplements (3.5% wt/wt) to a diet containing 80% lucerne and 20% barley on rumen fermentation and lipid metabolism in an artificial rumen (Rusitec). The experiment lasted 12 days with 6 days of stabilization period. The fatty acid (FA) supplementation to a mixed diet did not affect any parameters of rumen fermentation (degradation of DM, NDF, ADF, total VFA production, production of acetate, propionate and butyrate). The methane production was decreased numerically (NS) by FA supplements (OA, LA, and ALA by about 8, 8.3 and 13.2%, respectively). The stoichiometric parameters of rumen fermentation such as NM (nitrogen incorporated by microflora), OMF (organic matter fermented) and EMS (efficiency of microbial protein synthesis) were affected by unsaturated C18 FA to a different extent. EMS calculated from NM and OMF was significantly (<i>P</i> < 0.01) increased by OA, ALA and decreased (<i>P</i> < 0.01) by LA. The lipid metabolism was also affected by C18 FA supplements. The concentration of total FA and proportion of LCFA (long chain fatty acids, > C<sub>18:0</sub>) increased and proportion of MCFA (medium chain fatty acids, C<sub>14:0</sub> &minus; C<sub>17:0</sub>) decreased after OA, LA and ALA addition. The biohydrogenation (BH) of fatty acids was characterized by increased (NS) accumulation of stearic acid and trans isomers C18:1 and lower SFA/UFA ratio in the effluent. The concentrations of two main BH intermediates, TVA (trans 11 C<sub>18:1</sub>) and CLA (cis 9, trans 11 C<sub>18:2</sub>), significantly (<i>P</i> < 0.001) increased (TVA &minus; 1.06, 1.29 and 1.10; CLA &minus; 0.32, 0.43 and 0.36 mg/g rumen fluid DM, respectively) after OA, LA and ALA supplementation compared to the control (TVA &minus; 0.7; CLA &minus; 0.23).

Transcriptional regulation of bovine elongation of very long chain fatty acids protein 6 in lipid metabolism and adipocyte proliferation

2019 ◽  
Vol 120 (8) ◽  
pp. 13932-13943 ◽  
Author(s):  
Zainaguli Junjvlieke ◽  
Chu‐Gang Mei ◽  
Rajwali Khan ◽  
Wen‐Zhen Zhang ◽  
Jie‐Yun Hong ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Transcriptional Regulation ◽  
Lipid Metabolism ◽  
Long Chain Fatty Acids ◽  
Long Chain ◽  
Chain Fatty Acids

scholarly journals Epigenomics and Lipidomics Integration in Alzheimer Disease: Pathways Involved in Early Stages

Biomedicines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1812
Author(s):  
Carmen Peña-Bautista ◽  
Lourdes Álvarez-Sánchez ◽  
Antonio José Cañada-Martínez ◽  
Miguel Baquero ◽  
Consuelo Cháfer-Pericás
Keyword(s):  
Fatty Acids ◽  
Alzheimer Disease ◽  
Target Genes ◽  
Differentially Expressed ◽  
Long Chain Fatty Acids ◽  
Targeted Analysis ◽  
Fatty Acids Metabolism ◽  
Positive Correlations ◽  
Long Chain ◽  
Chain Fatty Acids

Background: Alzheimer Disease (AD) is the most prevalent dementia. However, the physiopathological mechanisms involved in its development are unclear. In this sense, a multi-omics approach could provide some progress. Methods: Epigenomic and lipidomic analysis were carried out in plasma samples from patients with mild cognitive impairment (MCI) due to AD (n = 22), and healthy controls (n = 5). Then, omics integration between microRNAs (miRNAs) and lipids was performed by Sparse Partial Least Squares (s-PLS) regression and target genes for the selected miRNAs were identified. Results: 25 miRNAs and 25 lipids with higher loadings in the sPLS regression were selected. Lipids from phosphatidylethanolamines (PE), lysophosphatidylcholines (LPC), ceramides, phosphatidylcholines (PC), triglycerides (TG) and several long chain fatty acids families were identified as differentially expressed in AD. Among them, several fatty acids showed strong positive correlations with miRNAs studied. In fact, these miRNAs regulated genes implied in fatty acids metabolism, as elongation of very long-chain fatty acids (ELOVL), and fatty acid desaturases (FADs). Conclusions: The lipidomic–epigenomic integration showed that several lipids and miRNAs were differentially expressed in AD, being the fatty acids mechanisms potentially involved in the disease development. However, further work about targeted analysis should be carried out in a larger cohort, in order to validate these preliminary results and study the proposed pathways in detail.

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.

Sign in / Sign up

Export Citation Format

Share Document