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Impact of Probiotics on Human Gut Microbiota and the Relationship with Obesity
Published in Marcela Albuquerque Cavalcanti de Albuquerque, Alejandra de Moreno de LeBlanc, Jean Guy LeBlanc, Raquel Bedani, Lactic Acid Bacteria, 2020
Fernanda Bianchi, Katia Sivieri
It has been suggested that the modulation of the expression of genes involved in inflammation and fatty acid oxidation, such as tumour necrosis factor alpha (TNFα), Interleukin 6 (IL6), PPARγ coactivator-1 alpha (PGC1α), IL1B, chemokine ligand 2 (CCL2), Carnitine palmitoyltransferase I and II (CPT1 and CPT2), and Acyl-CoA Oxidase 1 (ACOX1), are the most frequently-involved mechanisms in the probiotic’s anti-obesity effects. The exact genes modulated are dependent on the strain (Park et al. 2013, Miyoshi et al. 2014).
Mitochondrial Dysfunction and Oxidative Stress in the Pathogenesis of Metabolic Syndrome
Published in Shamim I. Ahmad, Handbook of Mitochondrial Dysfunction, 2019
FA derivatives from lipolysis, lipogenesis or FA catabolism are ligands of PPARa. Free fatty acids, including long-chain polyunsaturated FAs (LCPUFAs) and n-3 LCPUFAs, bind and activate the PPAR signaling to regulate the transcription of a cluster of genes involved in lipid and lipoprotein metabolism, FA β-oxidation in tissues with high oxidative rates, such as heart, liver, and muscle. Substrates of acyl-CoA oxidase 1 (ACOX1), the first rate-limiting peroxisomal β-oxidation enzyme, may also serve as PPARα agonists. Hydrolysis of hepatic intracellular triglyceride also yields lipid ligands for PPARa83. A range of synthetic PPARα agonists, including gemfibrozil, fenofibrate and ciprofibrate, have been synthesized and used in the treatment of primary hypertriglyceridemia or complexed dyslipidaemia84 in clinical.
Inhibiting Insulin Resistance and Accumulation of Triglycerides and Cholesterol in the Liver
Published in Christophe Wiart, Medicinal Plants in Asia for Metabolic Syndrome, 2017
Ethanol extract of aerial parts of Angelica keiskei Koidz. given for 11 weeks as 3% w/w of diet of to Wistar rats given 15% fructose solution as drinking water lowered liver weight compared to untreated animals.364 This supplementation lowered blood glucose by 16.5%, insulinaemia by 47.3% and insulin resistance.364 In regards to serum lipids, the treatment lowered triglycerides by 24.2%.364 This extract had no effect on plasma cholesterol but increased high-density lipoprotein–cholesterol from 33.9 to 48.6 mg/dL.364 Serum adiponectin was increased by the supplementation.364 At the hepatic level, the supplementation increased the expression of acyl-CoA oxidase and medium chain acyl-CoA dehydrogenase which are involved in fatty acid β-oxidation in peroxisomes and mitochondria respectively, carnitine palmitoyltransferase-1, key enzyme transport of fatty acids in mitochondria, and apolipoprotein A1 and ATP-binding cassette A1 which are both involved in high-density lipoprotein production364 which are downstream of peroxisome proliferator-activated receptor-α. This regimen had no effect on peroxisome proliferator-activated receptor-α expression in the liver364 suggesting a possible agonistic activity on this nuclear receptor by a constituent of yet unidentified.
PPARγ induces PD-L1 expression in MSS+ colorectal cancer cells
Published in OncoImmunology, 2021
Tobias Gutting, Veronika Hauber, Jens Pahl, Kay Klapproth, Wenyue Wu, Ioana Dobrota, Frank Herweck, Juliane Reichling, Laura Helm, Torsten Schroeder, Beifang Li, Philip Weidner, Tianzuo Zhan, Maximilian Eckardt, Johannes Betge, Sebastian Belle, Carsten Sticht, Timo Gaiser, Michael Boutros, Matthias P.A. Ebert, Adelheid Cerwenka, Elke Burgermeister
To decide if PD-L1 promoter activation is mediated through the receptor itself or off-target effects of the agonist(s), HT29 and HCT116 cells were transfected with empty vector (EV) or an expression plasmid encoding a dominant-negative (DN) PPARγ mutant and stimulated with rosi as earlier. This mutant was deficient in heterodimerization with retinoid X receptor (RXR) and DNA-binding due to deletion of the “D-box” docking motif in the transition region of the second zinc finger of the DBD and the hinge region (ΔDbox).36 As expected, luciferase activity was abrogated under these conditions (*p < .05 vs. vehicle or EV, two-way ANOVA with Bonferroni posttests, n = 3 per cell line) (Figure 1d). The mutant also attenuated transcription driven by 3xPPREs in the enhancer region of the acyl-CoA oxidase (ACO) gene and of other bona fide PPARγ-target genes (S3b,c). These data indicated that PPARγ binds and transactivates the human PDL1 promoter.
Emerging drugs for the treatment of non-alcoholic steatohepatitis: a focused review of farnesoid X receptor agonists
Published in Expert Opinion on Emerging Drugs, 2020
Raj A. Shah, Naim Alkhouri, Kris V Kowdley
FXR is expressed highly in the liver, ileum, kidney, and adrenal glands, and has been found to play a key role in bile acid and lipid metabolism [3]. An overview of the effects of FXR relevant to NASH is shown in Figure 1. In hepatocytes, FXR induces expression of small heterodimer partner (SHP), an orphan family nuclear receptor, which leads to inhibited transcription of sterol regulatory element factor binding protein-1 c (SREBP-1 c) [66]. SREBP-1 c has been shown to play a role in upregulating enzymes responsible for lipogenesis [66]. FXR in ileal enterocytes upregulates expression of FGF-19, a protein that binds a fibroblast growth factor receptor 4 (FGFR4)/βKlotho receptor complex in hepatocytes [67]. FGF-19 activates hepatic glycogen and protein synthesis [68] while inhibiting bile acid synthesis [67]. FXR may also crosstalk with PPAR-α, evidenced by the discovery of a FXR response element in the promoter of the gene encoding PPAR-α along with demonstration of FXR agonism leading to increased PPAR-α expression [69]. Target genes of PPAR-α include medium-chain acyl-coenzyme a and acyl-CoA oxidase 1, which are rate-limiting enzymes for fatty acid beta oxidation pathways, indicating that PPAR-α upregulates fatty acid catabolism [70]. Additionally, PPAR-α has been shown to increase expression of FGF-21, which leads to enhanced expression of glucose transporter 1 in extrahepatic tissue, improving basal glucose uptake [70].
Administration timing and duration-dependent effects of sesamin isomers on lipid metabolism in rats
Published in Chronobiology International, 2020
Norifumi Tateishi, Satoshi Morita, Izumi Yamazaki, Hitoshi Okumura, Masaru Kominami, Sota Akazawa, Ayuta Funaki, Namino Tomimori, Tomohiro Rogi, Hiroshi Shibata, Shigenobu Shibata
With respect to triglyceride, SE tended to decrease liver triglycerides after administration at ZT23 (Figure 1c) or had no effect on serum triglycerides (Figure 1d). On the other hand, genes related to triglyceride metabolism in the liver were markedly affected by SE treatment. Gene expression of acyl-CoA dehydrogenase medium chain (Acadm, Figure 2d) and acyl-CoA oxidase 1 (Acox1, Figure 2e), which are members of enzymes involved in fatty acid beta-oxidation, were significantly higher in SE-treated liver when compared with that of CON. Fatty acid synthase (Fasn, Figure 2f), which contributes to fatty acid synthesis, was lower in SE-treated liver as compared with CON. There are no obvious differences between administration timings of SE. Although the influence of SE on the expression of these genes involved in triglyceride metabolism preferred to allow triglyceride parameters to be lower, we did not observe the effect under these test conditions.