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1.
Link between Lipid Second Messengers and Osmotic Stress in Plants.
Rodas-Junco, BA, Racagni-Di-Palma, GE, Canul-Chan, M, Usorach, J, Hernández-Sotomayor, SMT
International journal of molecular sciences. 2021;(5)
Abstract
Plants are subject to different types of stress, which consequently affect their growth and development. They have developed mechanisms for recognizing and processing an extracellular signal. Second messengers are transient molecules that modulate the physiological responses in plant cells under stress conditions. In this sense, it has been shown in various plant models that membrane lipids are substrates for the generation of second lipid messengers such as phosphoinositide, phosphatidic acid, sphingolipids, and lysophospholipids. In recent years, research on lipid second messengers has been moving toward using genetic and molecular approaches to reveal the molecular setting in which these molecules act in response to osmotic stress. In this sense, these studies have established that second messengers can transiently recruit target proteins to the membrane and, therefore, affect protein conformation, activity, and gene expression. This review summarizes recent advances in responses related to the link between lipid second messengers and osmotic stress in plant cells.
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Gluconeogenesis in Plants: A Key Interface between Organic Acid/Amino Acid/Lipid and Sugar Metabolism.
Walker, RP, Chen, ZH, Famiani, F
Molecules (Basel, Switzerland). 2021;(17)
Abstract
Gluconeogenesis is a key interface between organic acid/amino acid/lipid and sugar metabolism. The aims of this article are four-fold. First, to provide a concise overview of plant gluconeogenesis. Second, to emphasise the widespread occurrence of gluconeogenesis and its utilisation in diverse processes. Third, to stress the importance of the vacuolar storage and release of Krebs cycle acids/nitrogenous compounds, and of the role of gluconeogenesis and malic enzyme in this process. Fourth, to outline the contribution of fine control of enzyme activity to the coordinate-regulation of gluconeogenesis and malate metabolism, and the importance of cytosolic pH in this.
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3.
Effects of bariatric surgery on lipid-lipoprotein profile.
Piché, ME, Tardif, I, Auclair, A, Poirier, P
Metabolism: clinical and experimental. 2021;:154441
Abstract
Most patients with severe obesity will present some lipid-lipoprotein abnormalities. The atherogenic dyslipidemia associated with severe obesity is characterized by elevated fasting and postprandial triglyceride levels, low high-density lipoprotein cholesterol concentrations, and increased proportion of small and dense low-density lipoproteins. Bariatric surgery has been proven safe and successful in terms of long-term weight loss and improvement in obesity co-existing metabolic conditions including lipid-lipoprotein abnormalities. Nevertheless, bariatric surgery procedures are not all equivalent. We conducted a comprehensive critical analysis of the literature related to severe obesity, bariatric surgery and lipid-lipoprotein metabolism/profile. In this review, we described the metabolic impacts of different bariatric surgery procedures on the lipid-lipoprotein profile, and the mechanisms linking bariatric surgery and dyslipidemia remission based on recent epidemiological, clinical and preclinical studies. Further mechanistic studies are essential to assess the potential of bariatric/metabolic surgery in the management of lipid-lipoprotein abnormalities associated with severe obesity. Understanding the beneficial effects of various bariatric surgery procedures on the lipid-lipoprotein metabolism and profile may result in a wider acceptance of this strategy as a long-term metabolic treatment of lipid-lipoprotein abnormalities in severe obesity and help clinician to develop an individualized and optimal approach in the management of dyslipidemia associated with severe obesity. BRIEF SUMMARY Abnormal lipid-lipoprotein profile is frequent in patients with severe obesity. Significant improvements in lipid-lipoprotein profile following bariatric surgery occur early in the postoperative period, prior to weight loss, and persists throughout the follow-up. The mechanisms that facilitate the remission of dyslipidemia after bariatric surgery, may involve positive effects on adipose tissue distribution/function, insulin sensitivity, liver fat content/function and lipid-lipoprotein metabolism.
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Lipid Composition, Digestion, and Absorption Differences among Neonatal Feeding Strategies: Potential Implications for Intestinal Inflammation in Preterm Infants.
Burge, K, Vieira, F, Eckert, J, Chaaban, H
Nutrients. 2021;(2)
Abstract
Necrotizing enterocolitis (NEC) is a significant cause of morbidity and mortality in the neonatal population. Formula feeding is among the many risk factors for developing the condition, a practice often required in the cohort most often afflicted with NEC, preterm infants. While the virtues of many bioactive components of breast milk have been extolled, the ability to digest and assimilate the nutritional components of breast milk is often overlooked. The structure of formula differs from that of breast milk, both in lipid composition and chemical configuration. In addition, formula lacks a critical digestive enzyme produced by the mammary gland, bile salt-stimulated lipase (BSSL). The gastrointestinal system of premature infants is often incapable of secreting sufficient pancreatic enzymes for fat digestion, and pasteurization of donor milk (DM) has been shown to inactivate BSSL, among other important compounds. Incompletely digested lipids may oxidize and accumulate in the distal gut. These lipid fragments are thought to induce intestinal inflammation in the neonate, potentially hastening the development of diseases such as NEC. In this review, differences in breast milk, pasteurized DM, and formula lipids are highlighted, with a focus on the ability of those lipids to be digested and subsequently absorbed by neonates, especially those born prematurely and at risk for NEC.
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5.
The Classical, Yet Controversial, First Enzyme of Lipid Synthesis: Escherichia coli Acetyl-CoA Carboxylase.
Cronan, JE
Microbiology and molecular biology reviews : MMBR. 2021;(3):e0003221
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Abstract
Escherichia coli acetyl-CoA carboxylase (ACC), the enzyme responsible for synthesis of malonyl-CoA, the building block of fatty acid synthesis, is the paradigm bacterial ACC. Many reports on the structures and stoichiometry of the four subunits comprising the active enzyme as well as on regulation of ACC activity and expression have appeared in the almost 20 years since this subject was last reviewed. This review seeks to update and expand on these reports.
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Current Perspectives on the Attainment of Lipid Modification Goals Relating to the Use of Statins and Ezetimibe for the Prevention of Cardiovascular Disease in the United Kingdom.
Reynolds, TM, Pottle, A, Quoraishi, SH
Vascular health and risk management. 2021;:227-237
Abstract
Despite widespread evidence of the effectiveness of lipid modification for the reduction of cardiovascular disease (CVD) risk, lipid modification goals are commonly underachieved in the United Kingdom (UK). In order to understand current UK lipid management guidance and the corresponding attainment of recommended lipid lowering goals relating to treatment with statins and ezetimibe, a literature review was conducted using PubMed focusing on publications between January 2017 and February 2020 in order to capture the most up-to-date literature. Identified publications were reviewed against key clinical guidelines for lipid management in relation to CVD risk from the National Institute for Health and Care Excellence (NICE, CG181), the Scottish Intercollegiate Guidelines Network (SIGN, 149) and European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS). Cholesterol lowering goals are central to current lipid lowering therapy guidance, although specific goals vary depending on the guideline and patients' individual risk profile. Current guidance by NICE and SIGN specifies that treatment should achieve a greater than 40% reduction in non-high-density lipoprotein cholesterol (non-HDL-C) at 3 months of treatment, while the ESC/EAS place emphasis on the lowering of low-density lipoprotein (LDL-C) and total cholesterol. Yet, despite widespread availability of guidance and consistent messaging that lipid lowering goals should be ambitious, current evidence suggests a significant proportion of UK patients have sub-optimal reductions in cholesterol/non-HDL-C/LDL-C. The reasons for this are reported to be multifactorial, including a lack of compliance with guidelines, particularly regarding high-intensity statin prescribing, patient adherence, statin intolerance and statin reluctance as well as wider genetic factors. A number of possible strategies to improve current lipid management and attainment of lipid-lowering goals were identified, including improving the patient-healthcare professional partnership, conducting audits of local prescribing versus guidance, implementing plans for the refinement of current services and considering alternative options such as cost-effective single pill combinations for improving adherence.
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From Food to Genes: Transcriptional Regulation of Metabolism by Lipids and Carbohydrates.
Bravo-Ruiz, I, Medina, MÁ, Martínez-Poveda, B
Nutrients. 2021;(5)
Abstract
Lipids and carbohydrates regulate gene expression by means of molecules that sense these macronutrients and act as transcription factors. The peroxisome proliferator-activated receptor (PPAR), activated by some fatty acids or their derivatives, and the carbohydrate response element binding protein (ChREBP), activated by glucose-derived metabolites, play a key role in metabolic homeostasis, especially in glucose and lipid metabolism. Furthermore, the action of both factors in obesity, diabetes and fatty liver, as well as the pharmacological development in the treatment of these pathologies are indeed of high relevance. In this review we present an overview of the discovery, mechanism of activation and metabolic functions of these nutrient-dependent transcription factors in different tissues contexts, from the nutritional genomics perspective. The possibility of targeting these factors in pharmacological approaches is also discussed. Lipid and carbohydrate-dependent transcription factors are key players in the complex metabolic homeostasis, but these factors also drive an adaptive response to non-physiological situations, such as overeating. Possibly the decisive role of ChREBP and PPAR in metabolic regulation points to them as ideal therapeutic targets, but their pleiotropic functions in different tissues makes it difficult to "hit the mark".
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8.
Lipid Optimization in Lower Extremity Peripheral Arterial Disease.
Sucharitkul, PPJ, Jones, KL, Scott, DJA, Bailey, MA
Annals of vascular surgery. 2021;:542-554
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Abstract
AIMS: This review aims to explore the current guidance and issues surrounding lipid optimisation of patients with peripheral arterial disease (PAD). METHODS A narrative review of the global PAD guidance, specifically focusing on low density lipoprotein cholesterol (LDL-C) reduction methods including; 'treating to target', 'fire and forget' and LDL-C percentage reduction. Advanced literature searches were carried out in Pubmed and Google Scholar databases comparing most recent PAD lipid guidance. RESULTS PAD lipid guidance could be improved internationally to help clinicians implement the best lipid-reduction strategies for their patients and challenge the arbitrary 1.4 mmol/L LDL-C target in line with novel proprotein convertase subtilisin/kexin type 9 inhibitors trials. By educating primary and secondary care staff on the benefits of maximal lipid-reduction therapies, we can reduce major adverse cardiovascular events and major adverse limb events. Championing PAD community clinics may lead to earlier prevention. Research comparing lipid-reduction strategies in practice is needed to improve outcomes internationally, and ongoing practice audited to understand the extent of under-prescribing in PAD. CONCLUSIONS This review highlights the current PAD lipid-reduction treatments and the clarity issues of global guidance. Further research is needed to tackle ongoing mortality and morbidity rates in PAD patients against their better off cardiovascular disease (CVD) peers. MESH KEY TERMS "Cholesterol", "Hydroxymethylglutaryl-CoA Reductase Inhibitors", "Ezetimibe", "Evolocumab", "Alirocumab", "Peripheral Arterial Disease", "Vascular Disease", "Atherosclerosis", "Secondary Prevention", "Lipoprotein, LDL".
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Meta-Analysis of Intensive Lipid-Lowering Therapy in Patients With Polyvascular Disease.
Alkhalil, M, Kuzemczak, M, Whitehead, N, Kavvouras, C, Džavík, V
Journal of the American Heart Association. 2021;(5):e017948
Abstract
Background Polyvascular atherosclerotic disease is associated with an increased risk of future cardiovascular events. Intensive lipid-lowering therapy (ILT) may mitigate this risk. The aims of this study-level meta-analysis were to examine the effects of ILT in patients with polyvascular disease and whether baseline low-density lipoprotein cholesterol (LDL-C) may determine the level of benefit. Methods and Results Electronic databases were searched through January 2020 to identify randomized controlled trials of treatments targeting upregulation of LDL-C receptors (ie, statins, ezetimibe, and PCSK9 [proprotein convertase subtilisin-kexin type 9] inhibitors). The primary end point was major adverse vascular events as defined by the included studies. A total of 94 362 patients (14 821 [18.6%] with polyvascular disease) from 7 studies were included. In patients with monovascular disease, ILT was associated with a 13% reduction in the primary end point (rate ratio [RR] 0.87; 95% CI, 0.81-0.93 [P=0.0002]) (absolute RR, 1.8%) compared with less ILT, while patients with polyvascular disease had 15% relative RR (0.85; 95% CI, 0.80-0.90 [P<0.00001]) (absolute RR, 6.5%) (P=0.66 for interaction). When factoring LDL-C, unlike patients with monovascular disease, the relative benefits of ILT, compared with less ILT, in patients with polyvascular disease were comparable with LDL-C >100 mg/dL (RR, 0.85; 95% CI, 0.80-0.90 [P<0.00001]) and LDL-C <100 mg/dL (RR, 0.88; 95% CI, 0.81-0.96 [P=0.003]) (P=0.23 for interaction). Conclusions Patients with polyvascular disease experienced comparable benefits to those with monovascular disease in response to ILT. The benefits of ILT in patients with polyvascular disease were not dependent on baseline LDL-C, challenging the approach of using LDL-C as a prerequisite to commence ILT for this high-risk subgroup.
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Development of Lipid Nanoparticles for the Delivery of Macromolecules Based on the Molecular Design of pH-Sensitive Cationic Lipids.
Sato, Y
Chemical & pharmaceutical bulletin. 2021;(12):1141-1159
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Abstract
Considerable efforts have been made on the development of lipid nanoparticles (LNPs) for delivering of nucleic acids in LNP-based medicines, including a first-ever short interfering RNA (siRNA) medicine, Onpattro, and the mRNA vaccines against the coronavirus disease 2019 (COVID-19), which have been approved and are currently in use worldwide. The successful rational design of ionizable cationic lipids was a major breakthrough that dramatically increased delivery efficiency in this field. The LNPs would be expected to be useful as a platform technology for the delivery of various therapeutic modalities for genome editing and even for undiscovered therapeutic mechanisms. In this review, the current progress of my research, including the molecular design of pH-sensitive cationic lipids, their applications for various tissues and cell types, and for delivering various macromolecules, including siRNA, antisense oligonucleotide, mRNA, and the clustered regularly interspaced short palindromic repeats (CRISPR)-associated (Cas) system will be described. Mechanistic studies regarding relationships between the physicochemical properties of LNPs, drug delivery, and biosafety are also summarized. Furthermore, current issues that need to be addressed for next generation drug delivery systems are discussed.