Uptake of long-chain fatty acids plays pivotal roles in metabolic homeostasis and human physiology. Uptake rates must be controlled in an organ-specific fashion to balance storage with metabolic ...needs during transitions between fasted and fed states. Many obesity-associated diseases, such as insulin resistance in skeletal muscle, cardiac lipotoxicity, and hepatic steatosis, are thought to be driven by the overflow of fatty acids from adipose stores and the subsequent ectopic accumulation of lipids resulting in apoptosis, ER stress, and inactivation of the insulin receptor signaling cascade. Thus, it is of critical importance to understand the components that regulate the flux of fatty acid between the different organ systems. Cellular uptake of fatty acids by key metabolic organs, including the intestine, adipose tissue, muscle, heart, and liver, has been shown to be protein mediated and various unique combinations of fatty acid transport proteins (FATPs/SLC27A1–6) are expressed by all of these tissues. Here we review our current understanding of how FATPs can contribute to normal physiology and how FATP mutations as well as hypo- and hypermorphic changes contribute to disorders ranging from cardiac lipotoxicity to hepatosteatosis and ichthyosis. Ultimately, our increasing knowledge of FATP biology has the potential to lead to the development of new diagnostic tools and treatment options for some of the most pervasive chronic human disorders. This article is part of a Special Issue entitled Triglyceride Metabolism and Disease.
► Physiological fatty acids fluxes and Slc27 members. ► FATP transport mechanism/subcellular localization. ► Contribution of FATPs to insulin resistance and cardiovascular disease. ► Role of FATP4 in skin and hepatobiliary disorders. ► Polymorphisms and mutations in human FATP genes.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Long-chain fatty acids (LCFAs) are not only important metabolites but contribute to many cellular functions including activation of protein kinase C (PKC) isoforms and nuclear transcription factors ...such as peroxisome proliferator-activated receptors (PPAPs). To assert their diverse effects LCFAs have first to traverse the plasma membrane, a process that can occur either through diffusion or be mediated by proteins. Considerable evidence has accumulated to show that in addition to a diffusional component, the intestine, heart, adipose tissue, and the liver express a saturable and specific LCFA transport system. Identifying the postulated fatty acid transporters is of considerable importance, since both increased and decreased fatty acid uptake have been implicated in diseases such as type-2 diabetes and acute liver failure. Fatty acid transport proteins (FATPs/solute carrier family 27) are integral transmembrane proteins that enhance the uptake of long-chain and very long chain fatty acids into cells. In humans FATPs comprise a family of six highly homologous proteins, hsFATP1-6, which are found in all fatty acid-utilizing tissues of the body. This review will focus on a brief discussion of FATP expression patterns, regulation, structure, and mechanism of transport.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The International Classification of Retinopathy of Prematurity is a consensus statement that creates a standard nomenclature for classification of retinopathy of prematurity (ROP). It was initially ...published in 1984, expanded in 1987, and revisited in 2005. This article presents a third revision, the International Classification of Retinopathy of Prematurity, Third Edition (ICROP3), which is now required because of challenges such as: (1) concerns about subjectivity in critical elements of disease classification; (2) innovations in ophthalmic imaging; (3) novel pharmacologic therapies (e.g., anti-vascular endothelial growth factor agents) with unique regression and reactivation features after treatment compared with ablative therapies; and (4) recognition that patterns of ROP in some regions of the world do not fit neatly into the current classification system.
Review of evidence-based literature, along with expert consensus opinion.
International ROP expert committee assembled in March 2019 representing 17 countries and comprising 14 pediatric ophthalmologists and 20 retinal specialists, as well as 12 women and 22 men.
The committee was initially divided into 3 subcommittees-acute phase, regression or reactivation, and imaging-each of which used iterative videoconferences and an online message board to identify key challenges and approaches. Subsequently, the entire committee used iterative videoconferences, 2 in-person multiday meetings, and an online message board to develop consensus on classification.
Consensus statement.
The ICROP3 retains current definitions such as zone (location of disease), stage (appearance of disease at the avascular-vascular junction), and circumferential extent of disease. Major updates in the ICROP3 include refined classification metrics (e.g., posterior zone II, notch, subcategorization of stage 5, and recognition that a continuous spectrum of vascular abnormality exists from normal to plus disease). Updates also include the definition of aggressive ROP to replace aggressive-posterior ROP because of increasing recognition that aggressive disease may occur in larger preterm infants and beyond the posterior retina, particularly in regions of the world with limited resources. ROP regression and reactivation are described in detail, with additional description of long-term sequelae.
These principles may improve the quality and standardization of ROP care worldwide and may provide a foundation to improve research and clinical care.
Age-related macular degeneration (AMD) is thought to cause approximately 9% of all cases of blindness worldwide. In Germany, half of all cases of blindness and high-grade visual impairment are due to ...AMD. In this review, the main risk factors, clinical manifestations, and treatments of this disease are presented.
This review is based on pertinent publications retrieved by a selective search in PubMed for original articles and reviews, as well as on current position statements by the relevant specialty societies.
AMD is subdivided into early, intermediate, and late stages. The early stage is often asymptomatic; patients in the other two stages often have distorted vision or central visual field defects. The main risk factors are age, genetic predisposition, and nicotine consumption. The number of persons with early AMD in Germany rose from 5.7 million in 2002 to ca. 7 million in 2017. Late AMD is subdivided into the dry late form of the disease, for which there is no treatment at present, and the exudative late form, which can be treated with the intravitreal injection of VEGF inhibitors.
More research is needed on the dry late form of AMD in particular, which is currently untreatable. The treatment of the exudative late form with VEGF inhibitors is labor-intensive and requires a close collaboration of the patient, the ophthalmologist, and the primary care physician.
Long-chain fatty acids are both important metabolites as well as signaling molecules. Fatty acid transport proteins are key mediators of cellular fatty acid uptake and recent transgenic and knockout ...animal models have provided new insights into their contribution to energy homeostasis and to pathological processes, including obesity and insulin desensitization.
Nitrogen use efficiency in rapeseed. A review Bouchet, Anne-Sophie; Anne Laperche; Christine Bissuel-Belaygue ...
Agronomy for sustainable development,
06/2016, Volume:
36, Issue:
2
Journal Article
Peer reviewed
Open access
Mineral nitrogen fertilization has improved crop yield over the last century but has also caused air and water pollution. Reduction of nitrogen inputs and maintaining high yields are therefore ...essential to ensure a more sustainable agriculture. Improving the nitrogen use efficiency (NUE) of crops is therefore needed. Rapeseed, Brassica napus, depends on nitrogen fertilization due to its low NUE, with the ratio of plant nitrogen content to nitrogen supplied often not exceeding 60Â %. Here, we review the major phenotypic traits associated with NUE in B. napus, with special emphasis on winter oilseed rape. We discuss the genetic diversity available and potential breeding strategies. The major points are the following: (1) rapeseed seed yield elaboration is complex, with overlapping phases of nitrogen uptake and remobilization during the crop cycle; (2) traits related to nitrogen uptake, such as root length and the amount of nitrogen absorbed after flowering, and traits related to nitrogen remobilization, such as the âstay-greenâ phenotype, have been identified as possible levers to improve NUE in rapeseed; (3) a substantial body of studies investigating the genetic control of NUE traits have already published and potential candidate genes identified; and (4) rapeseed genetic diversity may be enriched by exploiting interpopulation genetic variation and the closely related gene pools of Brassica rapa and Brassica oleracea.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Copper is a required metal nutrient for life, but global or local alterations in its homeostasis are linked to diseases spanning genetic and metabolic disorders to cancer and neurodegeneration. ...Technologies that enable longitudinal in vivo monitoring of dynamic copper pools can help meet the need to study the complex interplay between copper status, health, and disease in the same living organism over time. Here, we present the synthesis, characterization, and in vivo imaging applications of Copper-Caged Luciferin-1 (CCL-1), a bioluminescent reporter for tissue-specific copper visualization in living animals. CCL-1 uses a selective copper(I)-dependent oxidative cleavage reaction to release D-luciferin for subsequent bioluminescent reaction with firefly luciferase. The probe can detect physiological changes in labile Cu⁺ levels in live cells and mice under situations of copper deficiency or overload. Application of CCL-1 to mice with liver-specific luciferase expression in a diet-induced model of nonalcoholic fatty liver disease reveals onset of hepatic copper deficiency and altered expression levels of central copper trafficking proteins that accompany symptoms of glucose intolerance and weight gain. The data connect copper dysregulation to metabolic liver disease and provide a starting point for expanding the toolbox of reactivity-based chemical reporters for cell-and tissue-specific in vivo imaging.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Traumatic optic nerve injury may lead to almost instantaneous blindness. We describe a case of sight loss after a perforating injury to the eye. The case is unusual in that the patient remained ...conscious and the trauma to the eye was isolated. A full ophthalmological examination was therefore possible within hours as well as early magnetic resonance imaging of the facial skull. High-quality T1-weighted, T2-weighted, and diffusion-weighted imaging could be acquired. The latter included apparent diffusion coefficient maps. There was a loss of the subarachnoid space of the optic nerve, fluid in the retrobulbar fat of the affected eye, and signal changes in the optic nerve. Previous work has been contradictory on the signal of the optic nerve on apparent diffusion coefficient maps in sight loss, with an increase seen by one group and a decrease seen by another. Signal loss on the apparent diffusion coefficient map was seen in the case described here. Signal loss on apparent diffusion coefficient maps may thus be used as a surrogate marker of sight loss in patients who are unconscious or otherwise unable to cooperate in ophthalmological exams.
Organ-on-a-chip systems possess a promising future as drug screening assays and as testbeds for disease modeling in the context of both single-organ systems and multi-organ-chips. Although it ...comprises approximately one fourth of the body weight of a healthy human, an organ frequently overlooked in this context is white adipose tissue (WAT). WAT-on-a-chip systems are required to create safety profiles of a large number of drugs due to their interactions with adipose tissue and other organs
via
paracrine signals, fatty acid release, and drug levels through sequestration. We report a WAT-on-a-chip system with a footprint of less than 1 mm
2
consisting of a separate media channel and WAT chamber connected
via
small micropores. Analogous to the
in vivo
blood circulation, convective transport is thereby confined to the vasculature-like structures and the tissues protected from shear stresses. Numerical and analytical modeling revealed that the flow rates in the WAT chambers are less than 1/100 of the input flow rate. Using optimized injection parameters, we were able to inject pre-adipocytes, which subsequently formed adipose tissue featuring fully functional lipid metabolism. The physiologically relevant microfluidic environment of the WAT-chip supported long term culture of the functional adipose tissue for more than two weeks. Due to its physiological, highly controlled, and computationally predictable character, the system has the potential to be a powerful tool for the study of adipose tissue associated diseases such as obesity and type 2 diabetes.
Organs-on-a-chip possess a promising future as drug screening assays and testbeds for disease modeling in the context of both single-organ systems and multi-organ-chips.
Myeloid cells such as resident retinal microglia (MG) or infiltrating blood‐derived macrophages (Mϕ) accumulate in areas of retinal ischemia and neovascularization (RNV) and modulate neovascular eye ...disease. Their temporospatial distribution and biological function in this process, however, remain unclarified. Using state‐of‐the‐art methods, including cell‐specific reporter mice and high‐throughput RNA sequencing (RNA Seq), this study determined the extent of MG proliferation and Mϕ infiltration in areas with retinal ischemia and RNV in Cx3cr1CreERT2:Rosa26‐tdTomato mice and examined the transcriptional profile of MG in the mouse model of oxygen‐induced retinopathy (OIR). For RNA Seq, tdTomato‐positive retinal MG were sorted by flow cytometry followed by Gene ontology (GO) cluster analysis. Furthermore, intraperitoneal injections of the cell proliferation marker 5‐ethynyl‐2′‐deoxyuridine (EdU) were performed from postnatal day (p) 12 to p16. We found that MG is the predominant myeloid cell population while Mϕ rarely appears in areas of RNV. Thirty percent of retinal MG in areas of RNV were EdU‐positive indicating a considerable local MG cell expansion. GO cluster analysis revealed an enrichment of clusters related to cell division, tubulin binding, ATPase activity, protein kinase regulatory activity, and chemokine receptor binding in MG in the OIR model compared to untreated controls. In conclusion, activated retinal MG alter their transcriptional profile, exhibit considerable proliferative ability and are by far the most frequent myeloid cell population in areas of ischemia and RNV in the OIR model thus presenting a potential target for future therapeutic approaches.
Main points
Resident microglia are the dominant myeloid cell population accumulating in areas of retinal ischemia.
Activated microglia alter their transcriptional profile and exhibit proliferative ability thus presenting a target for therapeutic approaches.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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