Peroxisome proliferator-activated receptor (PPAR) represents an important member of the nuclear hormone receptor superfamily that can be activated by a variety of natural fatty acids, some of their metabolites and by commonly-used anti-lipidaemic drugs. We recently demonstrated PPAR expression in T lymphocytes, where it controls the initiation of transcription of T-box expressed in T-cells (T-bet) independent of added agonist. T-bet is an activation-inducible transcription factor regulator of interleukin 2 (suppression) and interferon (stimulation) synthesis. A suppressed ability to produce interleukin 2 and an enhanced production of interferon occurs in activated T-cells from PPAR-/- mice, as well as in T-cells from wild-type aged animals whose lymphocytes express lowered basal levels of PPAR. The dysregulated expression and/or function of cytokines, glucocorticoids or leptin that occurs with advanced age could all be responsible for the reduced expression of PPAR. Dietary supplementation of aged mice with vitamin E, or supplementation with known agonists of PPAR, was associated with elevation of lymphocyte expression of this nuclear hormone receptor, restoration of control over T-bet expression and elimination of the dysregulated production of interleukin 2 and interferon following lymphocyte activation. Interleukin 2 and interferon play very important roles in the initiation and/or regulation of immune, inflammatory and autoimmune disease states. Thus, the mechanisms that control the timing, magnitude and duration of specific cytokine production by activated T lymphocytes need clarification before appropriate nutritional or therapeutic strategies can be devised to treat disease conditions where cytokine expression and/or activities are deemed to be dysregulated and responsible.
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http://dx.doi.org/10.1079/pns2002173 | DOI Listing |
Curr Med Chem
January 2025
Transplant Research Center, Clinical Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
Nonalcoholic fatty liver disease (NAFLD) is one of the main causes of chronic liver disorders following liver transplantation. The prorenin receptor (PRR) plays a role in glucose and lipid metabolism, and the hepatic dysregulation of PRR is associated with the upregulation of several molecular pathways, such as the mammalian target of rapamycin (mTOR) and Peroxisome proliferator-activated receptor (PPAR) that promotes hepatic lipogenesis and leads to lipid accumulation in hepatocytes by upregulation of lipogenic genes. PRR inhibition leads to a reduction in the hepatic expression of sortilin-1 and low-density lipoprotein receptor (LDLR) levels and down-regulation of pyruvate dehydrogenase (PDH) and acetyl-CoA carboxylase (ACC) and reduces fatty acids synthesis in hepatocytes.
View Article and Find Full Text PDFCurr Opin Clin Nutr Metab Care
December 2024
Nutrition Foundation of Italy, Milan, Italy.
Purpose Of Review: This paper reviews the most recent literature from January 2023 to August 2024 on the physiological effects of n-6 polyunsaturated fatty acids (PUFAs), with a focus on linoleic acid (LA).
Recent Findings: Contrary to previous concerns that high LA intake may increase inflammation, most recent evidence supports the benefits of LA for cardiometabolic health. Several large studies report that higher blood LA levels correlate with reduced risks of coronary heart disease, stroke, and type 2 diabetes.
Nat Commun
January 2025
Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241, China.
Energy deprivation and metabolic rewiring of cardiomyocytes are widely recognized hallmarks of heart failure. Here, we report that HEY2 (a Hairy/Enhancer-of-split-related transcriptional repressor) is upregulated in hearts of patients with dilated cardiomyopathy. Induced Hey2 expression in zebrafish hearts or mammalian cardiomyocytes impairs mitochondrial respiration, accompanied by elevated ROS, resulting in cardiomyocyte apoptosis and heart failure.
View Article and Find Full Text PDFMol Metab
December 2024
Nutrition, Metabolism and Genomics Group, Division of Human Nutrition and Health, Wageningen University, Stippeneng 4, 6708 WE Wageningen, the Netherlands; Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853, USA. Electronic address:
The peroxisome proliferator-activated receptor-alpha (PPARα) plays a central role in lipid metabolism in the liver by stimulating the expression of hundreds of genes. Accordingly, regulation by PPARα could be a screening tool to identify novel genes involved in hepatic lipid metabolism. Previously, the mitochondrial transporter SLC25A47 was suggested to play a role in energy metabolism and liver-specific uncoupling, but further research is lacking.
View Article and Find Full Text PDFJ Agric Food Chem
January 2025
Laboratory of Functional Chemistry and Nutrition of Food, College of Food Science and Engineering, Northwest A&F University, Yangling, Shaanxi 712100, China.
Plant-based foods with low methionine contents have gained increasing interest for their potential health benefits, including neuroprotective effects. Methionine restriction (MR) linked to a plant-based diet has been shown to mitigate neurodegenerative diseases such as Alzheimer's disease (AD) through mechanisms that involve the gut microbiota. In this study, a 16-week MR diet (0.
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