1,720,995 research outputs found
Human health risk assessment for peroxisome proliferators: More than 30 years of research
No full textSubstances like gemfibrozil, clofibrate and fenofibrate, widely used in human care for their hypolipidemic effects, belong to a larger class of chemicals called peroxisome proliferators (PPs). PPs, by binding and activing the peroxisome proliferator-activated receptor α (PPARα), modulate gene involved in lipid homeostasis both in human and in rodent. In a different way, long term administration of PPs results in hepatocarcinogenesis only in rodent. Although the phenomenon is known since more than 30 years, the exact mechanism is not well understood and the human health risks are not established. In this mini-review is inspected the major findings done in the different species and illustrates the possible doubts for human health by the use of PPs. © 2008 Elsevier GmbH. All rights reserved
PPARα signaling is activated by cocoa in mouse liver
No full textIn this study we evaluated in mouse liver the effects of cocoa on PPARα signaling. To this aim, mouse diet was supplemented with 10%, w/w, cocoa for one and two weeks. We quantified the expression of PPARα target genes and PPARα gene level and some parameters related to PPARα activation (hepatosomatic index, peroxisomal β-oxidation system and catalase activity). Moreover, we evaluated antioxidant capacity of cocoa by detecting the expression of CAT and SOD1 genes (known to be involved in oxidative balance) and hypolipidemic properties on serum triglycerides. We made a parallel treatment with 0.025%, w/w, ciprofibrate, a well-known PPARα activator, to quantify signal modulation by cocoa. It is known that PPARα activation by ciprofibrate is mediated by direct binding to the receptor and strongly induces expression of target genes. Our results show that cocoa weakly up-regulates PPARα target genes as a consequence of the modulation of the PPARα gene level and does not improve the triglyceride profile in blood. Finally, cocoa increased SOD1 gene expression suggesting an antioxidant effect
Altered vitamin B12 metabolism in the central nervous system is associated with the modification of ribosomal gene expression: new insights from comparative RNA dataset analysis
Full text linkRecent studies have confirmed the direct role of vitamin B12 (VitB12) in the central nervous system (CNS) homeostasis; nevertheless, the detailed mechanisms are poorly understood. By analyzing RNA-Seq and microarray datasets obtained from databanks, this study aims to identify possible basic mechanisms, related to the brain, involved in altering the gene expression under VitB12 deficiency mimicking conditions. The database inquiry returned datasets generated from distinctly heterogeneous experimental sets and considering the quality and relevance requirements, two datasets from mouse and one from rat models were selected. The analyses of individual datasets highlighted a change in ribosomal gene expression in VitB12 deficiency mimicking conditions within each system. Specifically, a divergent regulation was observed depending on the animal model: mice showed a down regulation of the ribosomal gene expression, while rats an upregulation. Interestingly, E2f1 was significantly upregulated under VitB12 deficiency mimicking conditions in the animal models, with a greater upregulation in rats. The rat model also revealed putative E2F1 Transcription Factor Binding Sites (TFBSs) in the promoter of the differently regulated genes involved in ribosomal gene expression. This suggested the possibility that E2F1, being greater expressed in rats, could activate the ribosomal genes having E2F1 TFBSs, thus giving a plausible explication to the divergent regulation observed in animal models. Despite the great diversity of the experimental sets used to generate the datasets considered, a common alteration of the ribosomes exists, thereby indicating a possible basic and conserved response to VitB12 deficiency. Moreover, these findings could provide new insights on E2F1 and its association with CNS homeostasis and VitB12 deficiency
Contenuto di polifenoli e potere antiossidante di alcune bevande alcoliche e analcoliche
No full textNeural Stem Cells and Nutrients: Poised Between Quiescence and Exhaustion
No full textAdult neurogenesis initiated by neural stem cells (NSCs) contributes to brain homeostasis, damage repair, and cognition. Energy metabolism plays a pivotal role in neurogenic cell fate decisions regarding self-renewal, expansion and multilineage differentiation. NSCs need to fine-tune quiescence and proliferation/commitment to guarantee lifelong neurogenesis and avoid premature exhaustion. Accumulating evidence supports a model whereby calorie restriction or increased energy expenditure reinforce NSC quiescence and promote self-renewal. Conversely, growth/proliferation inputs and anabolic signals, although necessary for neurogenesis, deplete the NSCs pool in the long run. This framework incorporates the emerging neurogenic roles of nutrient-sensing signaling pathways, providing a rationale for the alarming connection between nutritional imbalances, metabolic disorders and accelerated brain aging
Enzymatic extraction of carotenoids from plant material using two immiscible liquid phases
No full textNutrients, neurogenesis and brain ageing: From disease mechanisms to therapeutic opportunities
No full textAppreciation of the physiological relevance of mammalian adult neurogenesis has in recent years rapidly expanded from a phenomenon of homeostatic cell replacement and brain repair to the current view of a complex process involved in high order cognitive functions. In parallel, an array of endogenous or exogenous triggers of neurogenesis has also been identified, among which metabolic and nutritional cues have drawn significant attention. Converging evidence from animal and in vitro studies points to nutrient sensing and energy metabolism as major physiological determinants of neural stem cell fate, and modulators of the whole neurogenic process. While the cellular and molecular circuitries underlying metabolic regulation of neurogenesis are still incompletely understood, the key role of mitochondrial activity and dynamics, and the importance of autophagy have begun to be fully appreciated; moreover, nutrient-sensitive pathways and transducers such as the insulin-IGF cascade, the AMPK/mTOR axis and the transcription regulators CREB and Sirt-1 have been included, beside more established “developmental” signals like Notch and Wnt, in the molecular networks that dictate neural-stem-cell self-renewal, migration and differentiation in response to local and systemic inputs. Many of these nutrient-related cascades are deregulated in the contest of metabolic diseases and in ageing, and may contribute to impaired neurogenesis and thus to cognition defects observed in these conditions. Importantly, accumulating knowledge on the metabolic control of neurogenesis provides a theoretical framework for the trial of new or repurposed drugs capable of interfering with nutrient sensing as enhancers of neurogenesis in the context of neurodegeneration and brain senescence
Neuroprotective Properties of Peroxisome Proliferator-Activated Receptor Alpha (PPARα) and its Lipid Ligands.
No full textSignalling lipids are known to control a wide array of cellular processes, including cell proliferation, apoptosis, migration, and energy metabolism. Fatty acids and their derivatives, eicosanoids, phosphoinositides, sphingolipids, some cannabinoid-like molecules bind and activate nuclear receptors, including peroxisome proliferator-activated receptors (PPARs). This subfamily of transcription factors comprise three isotypes - PPARα(NR1C1), PPAR α (NR1C2), PPARα (NR1C3) - which bind to specific DNA response elements, as heterodimers with retinoid X receptors. PPAR activity is modulated by post-translational modifications and cofactors, towards which they show differential affinity. The three PPARs mutually interact, being integrated in a complex system, leading to the concept of a "PPAR triad". Nevertheless, the isotypes also show distinct actions on cellular physiology and partially different tissue, ligand and target gene specificities. In the brain, while the functions of PPARγ and its ligands are being thoroughly investigated, the actual and potential roles of PPARα and δ are far from being clarified. PPARα appears especially intriguing, since it is selectively expressed in certain brain areas and neuronal/glial populations, and modulates antioxidant responses, neurotransmission, neuroinflammation, neurogenesis, and glial cell proliferation/differentiation. This receptor and its endogenous ligands, including oleoylethanoloamide (OEA) and palmitoylethanolamide (PEA), are involved in physiological and pathological responses, such as satiety, memory consolidation, and modulation of pain perception. The protective role of PPARα agonists in neurodegenerative diseases and in neuropsychiatric disorders makes manipulation of this pathway highly attractive as therapeutic strategy for neuropathological conditions. In this review, we focus on the pleiotropic functions of PPARα and its lipid ligands in the nervous tissue, devoting special attention to neuroprotection
Neuroprotective properties of peroxisome proliferator-activated receptor alpha (PPARα) and its lipid ligands
No full textSignalling lipids are known to control a wide array of cellular processes, including cell proliferation, apoptosis, migration, and energy metabolism. Fatty acids and their derivatives, eicosanoids, phosphoinositides, sphingolipids, some cannabinoid-like molecules bind and activate nuclear receptors, including peroxisome proliferator-activated receptors (PPARs). This subfamily of transcription factors comprises three isotypes - PPARα (NR1C1), PPAR β/δ (NR1C2), PPARγ (NR1C3) - which bind to specific DNA response elements, as heterodimers with retinoid X receptors. PPAR activity is modulated by post-translational modifications and cofactors, towards which they show differential affinity. The three PPARs mutually interact, being integrated in a complex system, leading to the concept of a "PPAR triad". Nevertheless, the isotypes also show distinct actions on cellular physiology and partially different tissue, ligand and target gene specificities. In the brain, while the functions of PPARγ and its ligands are being thoroughly investigated, the actual and potential roles of PPARα and β/δ are far from being clarified. PPARα appears especially intriguing, since it is selectively expressed in certain brain areas and neuronal/glial populations, and modulates antioxidant responses, neurotransmission, neuroinflammation, neurogenesis, and glial cell proliferation/differentiation. This receptor and its endogenous ligands, including oleoylethanoloamide (OEA) and palmitoylethanolamide (PEA), are involved in physiological and pathological responses, such as satiety, memory consolidation, and modulation of pain perception. The protective role of PPARα agonists in neurodegenerative diseases and in neuropsychiatric disorders makes manipulation of this pathway highly attractive as therapeutic strategy for neuropathological conditions. In this review, we focus on the pleiotropic functions of PPARα and its lipid ligands in the nervous tissue, devoting special attention to neuroprotection. © 2014 Bentham Science Publishers
Peroxisomes and peroxisomal disorders: The main facts
No full textInternational audienceThe importance of peroxisomes for human health is highlighted by the number of peroxisomal disorders (PDs), diseases associated to peroxisome biogenesis disorders and peroxisomal enzyme/transporter deficiencies. Currently, many physiological/biosynthetic mechanisms involved in these illnesses have been elucidated, but PDs remain incurable. This review examines the most important aspects concerning peroxisomes (i.e. Peroxisome proliferation, Peroxisome biogenesis, Metabolic functions of mammalian peroxisomes) and presents the most significant trends and advances in the study of peroxisomal disorders
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