Non-Alcoholic Fatty Liver Disease (NAFLD) is a common condition affecting around 10-25% of the general adult population, 15% of children, and even > 50% of individuals who have type 2 diabetes mellitus. It is a major cause of liver-related morbidity, and cardiovascular (CV) mortality is a common cause of death. In addition to being the initial step of irreversible alterations of the liver parenchyma causing cirrhosis, about 1/6 of those who develop NASH are at risk also developing CV disease (CVD). More recently the acronym MAFLD (Metabolic Associated Fatty Liver Disease) has been preferred by many European and US specialists, providing a clearer message on the metabolic etiology of the disease. The suggestions for the management of NAFLD are like those recommended by guidelines for CVD prevention. In this context, the general approach is to prescribe physical activity and dietary changes the effect weight loss. Lifestyle change in the NAFLD patient has been supplemented in some by the use of nutraceuticals, but the evidence based for these remains uncertain. The aim of this Position Paper was to summarize the clinical evidence relating to the effect of nutraceuticals on NAFLD-related parameters. Our reading of the data is that whilst many nutraceuticals have been studied in relation to NAFLD, none have sufficient evidence to recommend their routine use; robust trials are required to appropriately address efficacy and safety.

• MeSH
• diabetes mellitus 2. typu * komplikace   MeSH
• dítě MeSH
• dospělí MeSH
• jaterní cirhóza komplikace   MeSH
• kardiovaskulární nemoci * prevence a kontrola   MeSH
• lidé MeSH
• lipidy terapeutické užití   MeSH
• nealkoholová steatóza jater * farmakoterapie   MeSH
• potravní doplňky MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

AIM: The pathogenesis of obesity has been associated with high intake of dietary fat, and some recent studies have explored the cellular mechanisms of oro-sensory detection of dietary fatty acids. We further assessed the role of transient receptor potential canonical (TRPC) channels in oro-sensory perception of dietary lipids. METHODS: We determined by RT-qPCR and western blotting the expression of TRPC3/6/7 channels in mouse fungiform taste bud cells (mTBC). Immunocytochemistry was used to explore whether TRPC3 channels were co-expressed with fatty acid receptors. We employed wild-type (WT) mTBC, and those transfected with small interfering RNAs (siRNAs) against TRPC3 or STIM1. Ca2+ signalling was studied in TBC from TRPC3-/- mice and their WT littermates. RESULTS: We demonstrate that mouse fungiform taste bud cells (mTBC) express TRPC3, but not TRPC6 or TRPC7 channels, and their inactivation by siRNA or experiments on TBC from TRPC3-/- mice brought about a decrease in fatty acid-induced gustatory Ca2+ signalling, coupled with taste bud CD36 lipid sensor. TRPC3 channel activation was found to be under the control of STIM1 in lingual mTBC. Behavioural studies showed that spontaneous preference for a dietary long-chain fatty acid was abolished in TRPC3-/- mice, and in mice wherein lingual TRPC3 expression was silenced by employing siRNA. CONCLUSION: We report that lingual TRPC3 channels are critically involved in fat taste perception.

• MeSH
• chuťová percepce * MeSH
• dietní tuky MeSH
• kationtové kanály TRPC genetika   MeSH
• lipidy MeSH
• myši MeSH
• preference v jídle * MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The lipids in the mammalian stratum corneum (SC) adopt an unusually rigid arrangement to form a vital barrier preventing water loss and harmful environmental impacts. Just above the physiological temperature, a subset of barrier lipids undergoes a phase transition from a very tight orthorhombic to a looser hexagonal arrangement and vice versa. The purpose of this lipid transition in skin physiology is unknown. Permeability experiments on isolated human SC indicated that the transition affects the activation energy for a model compound that prefers lateral movement along lipid layers but not for water or a large polymer that would cross the SC through the pore pathway. The orthorhombic phase content of SC lipids, as determined by infrared spectroscopy, was also modulated by (de)hydration. Spontaneous rearrangement of human SC lipid monolayers into 10 nm higher multilamellar islets at 32-37 °C but not at room temperature was revealed by atomic force microscopy. Our findings add to our knowledge of fundamental skin physiology suggesting a fine temperature- and hydration-controlled switch from fluid lipids (required for lipid barrier assembly) to rigid and tightly packed lipids in the mature SC (necessary for the water and permeability barriers).

• MeSH
• epidermis * MeSH
• lidé MeSH
• lipidy MeSH
• nízká teplota * MeSH
• savci MeSH
• teplota MeSH
• voda MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

DivIVA is a protein initially identified as a spatial regulator of cell division in the model organism Bacillus subtilis, but its homologues are present in many other Gram-positive bacteria, including Clostridia species. Besides its role as topological regulator of the Min system during bacterial cell division, DivIVA is involved in chromosome segregation during sporulation, genetic competence, and cell wall synthesis. DivIVA localizes to regions of high membrane curvature, such as the cell poles and cell division site, where it recruits distinct binding partners. Previously, it was suggested that negative curvature sensing is the main mechanism by which DivIVA binds to these specific regions. Here, we show that Clostridioides difficile DivIVA binds preferably to membranes containing negatively charged phospholipids, especially cardiolipin. Strikingly, we observed that upon binding, DivIVA modifies the lipid distribution and induces changes to lipid bilayers containing cardiolipin. Our observations indicate that DivIVA might play a more complex and so far unknown active role during the formation of the cell division septal membrane.

• MeSH
• bakteriální proteiny metabolismus   MeSH
• buněčná membrána metabolismus   MeSH
• Clostridioides difficile růst a vývoj   metabolismus   MeSH
• kardiolipiny metabolismus   MeSH
• membránové lipidy metabolismus   MeSH
• proteiny buněčného cyklu metabolismus   MeSH
• transport proteinů MeSH
• Publikační typ
• časopisecké články MeSH

Despite advances in medical therapy and percutaneous revascularization, patients with acute coronary syndrome face a high risk of early, recurrent cardiovascular events. Interventions targeting atherogenic lipoproteins may favorably modify this risk. RECENT FINDINGS: Two randomized clinical trials, MIRACL and PROVE-IT, demonstrated efficacy of early, intensive statin therapy after acute coronary syndrome. Recent observational and meta-analyses corroborate the findings of these trials. The benefit of intensive statin treatment appears to apply broadly to elderly as well as younger patients, and to patients with or without diabetes or metabolic syndrome. Randomized trials demonstrating the efficacy of early, intensive statin treatment after acute coronary syndrome employed fixed statin dosages, and there does not appear to be an initial or achieved LDL-cholesterol level below which benefit is absent. As such, broad application of intensive statin therapy after acute coronary syndrome may be preferable to titration of statin dose to achieve specific LDL goals. Low HDL-cholesterol predicts risk after acute coronary syndrome; therefore, pharmacologic interventions to raise HDL concentration or mimic its function may help reduce that risk. SUMMARY: Early, intensive statin therapy is safe and effective after acute coronary syndrome. Future research will determine whether drugs that raise or mimic HDL-cholesterol are effective adjuncts to statin therapy.

• MeSH
• akutní koronární syndrom epidemiologie   farmakoterapie   metabolismus   MeSH
• anticholesteremika aplikace a dávkování   terapeutické užití   MeSH
• cholesterol metabolismus   MeSH
• lidé MeSH
• metabolismus lipidů účinky léků   MeSH
• randomizované kontrolované studie jako téma MeSH
• rizikové faktory MeSH
• Check Tag
• lidé MeSH

Oxidative stress is known to play an important role in the pathogenesis of Alzheimer's disease. Moreover, it is becoming increasingly evident that the plasma membrane of neurons plays a role in modulating the aggregation and toxicity of Alzheimer's amyloid-β peptide (Aβ). In this study, the combined and interdependent effects of oxidation and membrane interactions on the 42 residues long Aβ isoform are investigated using molecular simulations. Hamiltonian replica exchange molecular dynamics simulations are utilized to elucidate the impact of selected oxidized glycine residues of Aβ42 on the interactions of the peptide with a model membrane comprised of 70% POPC, 25% cholesterol, and 5% of the ganglioside GM1. The main findings are that, independent of the oxidation state, Aβ prefers binding to GM1 over POPC, which is further enhanced by the oxidation of Gly29 and Gly33 and reduced the formation of β-sheet. Our results suggest that the differences observed in Aβ42 conformations and its interaction with a lipid bilayer upon oxidation originate from the position of the oxidized Gly residue with respect to the hydrophobic sequence of Aβ42 involving the Gly29-XXX-Gly33-XXX-Gly37 motif and from specific interactions between the peptide and the terminal sugar groups of GM1.

• MeSH
• Alzheimerova nemoc metabolismus   MeSH
• amyloidní beta-protein chemie   metabolismus   MeSH
• buněčná membrána metabolismus   MeSH
• cholesterol metabolismus   MeSH
• hydrofobní a hydrofilní interakce MeSH
• lipidové dvojvrstvy metabolismus   MeSH
• membránové lipidy metabolismus   MeSH
• molekulární konformace MeSH
• neurony metabolismus   MeSH
• oxidační stres fyziologie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Benzalkonium chloride (BAK) compounds are commonly used in topical ophthalmic products as preservatives and stabilizers. BAK mixtures containing several compounds with different alkyl chain lengths are typically used. However, in chronic eye conditions, such as dry eye disease and glaucoma, the accumulation of adverse effects of BAKs was observed. Hence, preservative-free eye drops formulations are preferred. On the other hand, selected long-chain BAKs, particularly cetalkonium chloride, exhibit therapeutic functions, promoting epithelium wound healing and tear film stability. Nevertheless, the mechanism of BAKs influence on the tear film is not fully understood. By employing in vitro experimental and in silico simulation techniques, we elucidate the action of BAKs and demonstrate that long-chain BAKs accumulate in the lipid layer of the tear film model, stabilizing it in a concentration-dependent fashion. In contrast, short-chain BAKs interacting with the lipid layer compromise the tear film model stability. These findings are relevant for topical ophthalmic drug formulation and delivery in the context of selecting proper BAK species and understanding the dose dependency for tear film stability.

• MeSH
• benzalkoniové sloučeniny škodlivé účinky   MeSH
• konzervační prostředky farmaceutické * farmakologie   MeSH
• lidé MeSH
• lipidy farmakologie   MeSH
• oční roztoky MeSH
• slzy MeSH
• syndromy suchého oka * farmakoterapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Metabolic reprogramming of cancer cells is a common hallmark of malignant transformation. The preference for aerobic glycolysis over oxidative phosphorylation in tumors is a well-studied phenomenon known as the Warburg effect. Importantly, metabolic transformation of cancer cells also involves alterations in signaling cascades contributing to lipid metabolism, amino acid flux and synthesis, and utilization of ketone bodies. Also, redox regulation interacts with metabolic reprogramming during malignant transformation. Flavonoids, widely distributed phytochemicals in plants, exert various beneficial effects on human health through modulating molecular cascades altered in the pathological cancer phenotype. Recent evidence has identified numerous flavonoids as modulators of critical components of cancer metabolism and associated pathways interacting with metabolic cascades such as redox balance. Flavonoids affect lipid metabolism by regulating fatty acid synthase, redox balance by modulating nuclear factor-erythroid factor 2-related factor 2 (Nrf2) activity, or amino acid flux and synthesis by phosphoglycerate mutase 1. Here, we discuss recent preclinical evidence evaluating the impact of flavonoids on cancer metabolism, focusing on lipid and amino acid metabolic cascades, redox balance, and ketone bodies.

• MeSH
• aminokyseliny * MeSH
• faktor 2 související s NF-E2 metabolismus   MeSH
• flavonoidy farmakologie   MeSH
• ketolátky metabolismus   MeSH
• lidé MeSH
• metabolismus lipidů MeSH
• nádorová transformace buněk metabolismus   MeSH
• nádory * farmakoterapie   metabolismus   MeSH
• oxidace-redukce MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

BACKGROUND/OBJECTIVE: Obesity is an alarming threat for all age groups, including children. Fat overconsumption is one of the factors that directly influences this pathology. Recent studies have suggested that a common variant in the CD36 gene, that is, single-nucleotide polymorphism (SNP) rs1761667-A allele, that reduces CD36 expression, associates with high oral fat detection thresholds in some obese subjects. The objective was to assess fatty acid sensitivity in relation to CD36 SNP in young lean and obese children. SUBJECTS/METHODS: We studied lingual detection thresholds for emulsions, containing oleic acid, in Algerian children (n=116, age=8±0.5 years) who were divided into two groups: obese (n=57; body mass index (BMI) z-score=2.513±0.490) and lean children (n=59; BMI z-score=-0.138±0.601) by alternative-forced choice method. To correlate the lipid taste perception thresholds with CD36 SNP, the children were genotyped for A/G SNP rs1761667 in 5'UTR region of CD36 by using PCR and restriction fragment length polymorphism. RESULTS: We noticed significantly higher CD36 A-allele frequency (P=0.036) in young obese children compared with leans. CD36 A-allele was associated with higher lipid taste perception thresholds than G-allele in obese children, but not in lean controls. Moreover, waist circumference was positively correlated with reduced fat taste sensitivity in these children. CONCLUSIONS: CD36 SNP A-allele, being present both in young lean and in obese children, is associated with high threshold for fatty acid taste sensitivity only in obese children.

• MeSH
• antigeny CD36 genetika   MeSH
• chuťová percepce genetika   MeSH
• dietní tuky MeSH
• dítě MeSH
• frekvence genu MeSH
• genotyp MeSH
• hubenost genetika   metabolismus   MeSH
• index tělesné hmotnosti MeSH
• jednonukleotidový polymorfismus * MeSH
• kyselina olejová metabolismus   MeSH
• lidé MeSH
• obezita genetika   metabolismus   MeSH
• obvod pasu MeSH
• preference v jídle MeSH
• průzkumy a dotazníky MeSH
• stravovací zvyklosti MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Alžírsko MeSH

Recent studies have suggested that excessive intake of dietary fat is associated with obesity. Some obese subjects have been reported to exhibit high thresholds for the gustatory detection of lipids via lipid receptors, such as cluster of differentiation 36 (CD36). We studied lingual detection thresholds for emulsions containing oleic acid in obese Tunisian women (n 203) using a three-alternative forced choice (3-AFC) method. Genotyping of the TNF-α (rs1800629), IL-6 (rs1800795) and CD36 (rs1761667) genes was performed to associate with lipid taste perception thresholds. The CD36 genotype distribution was as follows: GG (n 42), AG (n 102) and AA (n 59). Women with the CD36 GG genotype exhibited oral detection thresholds for oleic acid that were more than three times lower than those with the CD36 AA genotype. The present study confirms a high threshold of gustatory fat detection in obese women with the CD36 AA genotype, but there is no significant association with the IL-6 and TNF-α gene polymorphisms.

• MeSH
• alely MeSH
• antigeny CD36 genetika   MeSH
• aplikace orální MeSH
• chuť genetika   MeSH
• chuťová percepce genetika   MeSH
• chuťové pohárky fyziologie   MeSH
• dietní tuky * MeSH
• dospělí MeSH
• genotyp MeSH
• interleukin-6 krev   MeSH
• jednonukleotidový polymorfismus MeSH
• kyselina olejová chemie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• obezita patofyziologie   MeSH
• preference v jídle MeSH
• shluková analýza MeSH
• TNF-alfa genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Tunisko MeSH