Oleic acid is a potent inhibitor of fatty acid and cholesterol synthesis in C6 glioma cells.

Glial cells play a pivotal role in brain fatty acid metabolism and membrane biogenesis. However, the potential regulation of lipogenesis and cholesterologenesis by fatty acids in glial cells has been barely investigated. Here, we show that physiologically relevant concentrations of various saturated, monounsaturated, and polyunsaturated fatty acids significantly reduce [1-(14)C]acetate incorporation into fatty acids and cholesterol in C6 cells. Oleic acid was the most effective at depressing lipogenesis and cholesterologenesis; a decreased label incorporation into cellular palmitic, stearic, and oleic acids was detected, suggesting that an enzymatic step(s) of de novo fatty acid biosynthesis was affected. To clarify this issue, the activities of acetyl-coenzyme A carboxylase (ACC) and FAS were determined with an in situ digitonin-permeabilized cell assay after incubation of C6 cells with fatty acids. ACC activity was strongly reduced ( approximately 80%) by oleic acid, whereas no significant change in FAS activity was observed. Oleic acid also reduced the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR). The inhibition of ACC and HMGCR activities is corroborated by the decreases in ACC and HMGCR mRNA abundance and protein levels. The downregulation of ACC and HMGCR activities and expression by oleic acid could contribute to the reduced lipogenesis and cholesterologenesis

Modulation of hepatic lipid metabolism by olive oil and its phenols in nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) represents the most common chronic liver disease in western countries, being considered the hepatic manifestation of metabolic syndrome. Cumulative lines of evidence suggest that olive oil, used as primary source of fat by Mediterranean populations, may play a key role in the observed health benefits on NAFLD. In this review, we summarize the state of the art of the knowledge on the protective role of both major and minor components of olive oil on lipid metabolism during NAFLD. In particular, the biochemical mechanisms responsible for the increase or decrease in hepatic lipid content are critically analyzed, taking into account that several studies have often provided different and/or conflicting results in animal models fed on olive oil-enriched diet. In addition, new findings that highlight the hypolipidemic and the antisteatotic actions of olive oil phenols are presented. As mitochondrial dysfunction plays a key role in the pathogenesis of NAFLD, the targeting of these organelles with olive oil phenols as a powerful therapeutic approach is also discussed

Oxidation of Hepatic Carnitine Palmitoyl Transferase-I (CPT-I) Impairs Fatty Acid Beta-Oxidation in Rats Fed a Methionine-Choline Deficient Diet

There is growing evidence that mitochondrial dysfunction, and more specifically fatty acid β-oxidation impairment, is involved in the pathophysiology of non-alcoholic steatohepatitis (NASH). The goal of the present study was to achieve more understanding on the modification/s of carnitinepalmitoyltransferase-I (CPT-I), the rate-limiting enzyme of the mitochondrial fatty acid β-oxidation, during steatohepatitis. A high fat/methionine-choline deficient (MCD) diet, administered for 4 weeks, was used to induce NASH in rats. We demonstrated that CPT-Iactivity decreased, to the same extent, both in isolated liver mitochondria and in digitonin-permeabilized hepatocytes from MCD-diet fed rats. At the same time, the rate of total fatty acid oxidation to CO2 and ketone bodies, measured in isolated hepatocytes, was significantly lowered in treated animals when compared to controls. Finally, an increase in CPT-I mRNA abundance and protein content, together with a high level of CPT-I protein oxidation was observed in treated rats. A posttranslational modification of rat CPT-I during steatohepatitis has been here discussed

Oral Microbiome and Preterm Birth: Correlation or Coincidence? A Narrative Review

AIM: Physiological changes that occur during pregnancy involve, as a natural consequence, also modifications of oral microbiome. However, the addition with microbial imbalance due to pre-existing periodontal infection might impair a pathological alteration in the phylogenetic community structure and composition in the oral cavity, exacerbating an inflammatory status, and becoming a potential risk factor for preterm birth. From the empirical findings about the relationship between periodontal pathogens and systemic diseases, a clear interest focused on the potential impact of some periodontal pathogens on the preterm birth risk has emerged. In this close emerging link, the potential interdependence existing between dysbiosis of oral microbiome and changes in maternal-fetal barrier in premature rupture of membranes was explored. MATERIALS AND METHODS: In accordance with Preferred Reporting Items for Systematic Reviews and Meta- Analyses guidelines, a Medline search was performed for studies focusing on oral microbioma and its association with pre-term birth, and completed by additional hand searching. Two reviewers independently selected studies and extracted data. The search was restricted to only reports written in English. RESULTS: The electronic search produced 66 items. Six duplicates were found. Among the collected studies, 56 were discarded because they met the exclusion criteria. The articles and reports in our review showed a connection between preterm birth and altered oral microbiome, suggesting a potential key role of Fusobacterium nucleatum, a notable periodontal pathogen involved in several pathological periodontal conditions, in increasing the risk of premature birth. CONCLUSIONS: Since F. nucleatum is frequently associated with preterm birth, it is coherent to hypothesize a potential role for the oral microbiota for preterm birth risk. Further studies should be carried out to determine the changes of the oral microflora in pregnancy and to provide comprehensive knowledge of the diversity of oral bacteria involved in preterm birth

Oral Microbiome and Preterm Birth: Correlation or Coincidence? A Narrative Review

BACKGROUND: Physiological changes that occur during pregnancy involve, as a natural consequence, also modifications of oral microbiome. However, the addition with microbial imbalance due to pre-existing periodontal infection might impair a pathological alteration in the phylogenetic community structure and composition in the oral cavity, exacerbating an inflammatory status, and becoming a potential risk factor for preterm birth. From the empirical findings about the relationship between periodontal pathogens and systemic diseases, a clear interest focused on the potential impact of some periodontal pathogens on the preterm birth risk has emerged. AIM: Exploration of the potential interdependence existing between dysbiosis of oral microbiome and changes in maternal-fetal barrier in premature rupture of membranes. MATERIALS AND METHODS: In accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a Medline search was performed for studies focusing on oral microbioma and its association with pre-term birth, and completed by additional hand searching. Two reviewers independently selected studies and extracted data. The search was restricted to only reports written in English. RESULTS: The electronic search produced 66 items. Six duplicates were found. Among the collected studies, 56 were discarded because they met the exclusion criteria. The articles and reports in our review showed a connection between preterm birth and altered oral microbiome, suggesting a potential key role of Fusobacterium nucleatum, a notable periodontal pathogen involved in several pathological periodontal conditions, in increasing the risk of premature birth. CONCLUSIONS: Since F. nucleatum is frequently associated with preterm birth, it is coherent to hypothesize a potential role for the oral microbiota for preterm birth risk. Further studies should be carried out to determine the changes of the oral microflora in pregnancy and to provide comprehensive knowledge of the diversity of oral bacteria involved in preterm birth

Oleic Acid and Hydroxytyrosol Inhibit Cholesterol and Fatty Acid Synthesis in C6 Glioma Cells

Recently, the discovery of natural compounds capable of modulating nervous system function has revealed new perspectives for a healthier brain. Here, we investigated the effects of oleic acid (OA) and hydroxytyrosol (HTyr), two important extra virgin olive oil compounds, on lipid synthesis in C6 glioma cells. OA and HTyr inhibited both de novo fatty acid and cholesterol syntheses without affecting cell viability. The inhibitory effect of the individual compounds was more pronounced if OA and HTyr were administered in combination. A reduction of polar lipid biosynthesis was also detected, while triglyceride synthesis was marginally affected. To clarify the lipid-lowering mechanism of these compounds, their effects on the activity of key enzymes of fatty acid biosynthesis (acetyl-CoA carboxylase-ACC and fatty acid synthase-FAS) and cholesterologenesis (3-hydroxy-3-methylglutaryl-CoA reductase-HMGCR) were investigated in situ by using digitonin-permeabilized C6 cells. ACC and HMGCR activities were especially reduced after 4 h of 25 μM OA and HTyr treatment. No change in FAS activity was observed. Inhibition of ACC and HMGCR activities is corroborated by the decrease of their mRNA abundance and protein level. Our results indicate a direct and rapid downregulatory effect of the two olive oil compounds on lipid synthesis in C6 cells

Hydroxyapatite–Silicon Scaffold Promotes Osteogenic Differentiation of CGF Primary Cells s

Simple Summary: The aim of this study was to identify new and innovative strategies to improve the tissue-regeneration process. Concentrated growth factor (CGF) is an autologous biomaterial rich in growth factors and multipotent stem cells. The purpose of our study was to evaluate the osteogenic differentiation of CGF primary cells in the presence of a hydroxyapatite–silicon scaffold, which represents a very interesting material in the field of bone reconstructive surgery. Our findings showed that the hydroxyapatite–silicon scaffold provided support to primary CGF cells by enhancing osteogenic differentiation. These data suggest interesting perspectives in the use of CGF together with scaffolds in the field of regenerative medicine. Abstract: The application of scaffolding materials together with stem cell technologies plays a key role in tissue regeneration. Therefore, in this study, CGF (concentrated growth factor), which represents an autologous and biocompatible blood-derived product rich in growth factors and multipotent stem cells, was used together with a hydroxyapatite and silicon (HA-Si) scaffold, which represents a very interesting material in the field of bone reconstructive surgery. The aim of this work was to evaluate the potential osteogenic differentiation of CGF primary cells induced by HASi scaffolds. The cellular viability of CGF primary cells cultured on HA-Si scaffolds and their structural characterization were performed by MTT assay and SEM analysis, respectively. Moreover, the matrix mineralization of CGF primary cells on the HA-Si scaffold was evaluated through Alizarin red staining. The expression of osteogenic differentiation markers was investigated through mRNA quantification by real-time PCR. We found that the HA-Si scaffold was not cytotoxic for CGF primary cells, allowing their growth and proliferation. Furthermore, the HASi scaffold was able to induce increased levels of osteogenic markers, decreased levels of stemness markers in these cells, and the formation of a mineralized matrix. In conclusion, our results suggest that HA-Si scaffolds can be used as a biomaterial support for CGF application in the field of tissue regeneration

Coffee Bioactive N-Methylpyridinium Attenuates Tumor Necrosis Factor (TNF)-α-Mediated Insulin Resistance and Inflammation in Human Adipocytes

Although coffee consumption has been historically associated with negative health outcomes, recent evidence suggests a lower risk of metabolic syndrome, obesity and diabetes among regular coffee drinkers. Among the plethora of minor organic compounds assessed as potential mediators of coffee health benefits, trigonelline and its pyrolysis product N-methylpyridinium (NMP) were preliminary shown to promote glucose uptake and exert anti-adipogenic properties. Against this background, we aimed at characterizing the effects of trigonelline and NMP in inflamed and dysfunctional human adipocytes. Human Simpson-Golabi-Behmel syndrome (SGBS) adipocytes were treated with NMP or, for comparison, trigonelline, for 5 h before stimulation with tumor necrosis factor (TNF)-α. NMP at concentrations as low as 1 µmol/L reduced the stimulated expression of several pro-inflammatory mediators, including C-C Motif chemokine ligand (CCL)-2, C-X-C Motif chemokine ligand (CXCL)-10, and intercellular adhesion Molecule (ICAM)-1, but left the induction of prostaglandin G/H synthase (PTGS)2, interleukin (IL)-1β, and colony stimulating factor (CSF)1 unaffected. Furthermore, NMP restored the downregulated expression of adiponectin (ADIPOQ). These effects were functionally associated with downregulation of the adhesion of monocytes to inflamed adipocytes. Under the same conditions, NMP also reversed the TNF-α-mediated suppression of insulin-stimulated Ser473 Akt phosphorylation and attenuated the induction of TNF-α-stimulated lipolysis restoring cell fat content. In an attempt to preliminarily explore the underlying mechanisms of its action, we show that NMP restores the expression of the master regulator of adipocyte differentiation peroxisome proliferator-activated receptor (PPAR)γ and downregulates activation of the pro-inflammatory mitogen-activated protein jun N-terminal kinase (JNK). In conclusion, NMP reduces adipose dysfunction in pro-inflammatory activated adipocytes. These data suggest that bioactive NMP in coffee may improve the inflammatory and dysmetabolic milieu associated with obesity

Assessment of Subjective Well-Being in a Cohort of University Students and Staff Members: Association with Physical Activity and Outdoor Leisure Time during the COVID-19 Pandemic

Time spent outdoors and physical activity (PA) promote mental health. To confirm this relationship in the aftermath of COVID-19 lockdowns, we explored individual levels of anxiety, depression, stress and subjective well-being (SWB) in a cohort of academic students and staff members and tested their association with sport practice, PA at leisure time and time spent outdoors. Our cross-sectional study collected data during the COVID-19 outbreak (April–May 2021) on 939 students and on 238 employees, who completed an online survey on sociodemographic and lifestyle features, depression, anxiety, stress, and SWB. Results showed that the students exhibited higher levels of anxiety, depression, and stress, and lower levels of SWB (p < 0.001 for all domains) compared to the staff members. Correlation analysis confirmed that PA and time spent in nature were associated to high mental health scores among staff and, more consistently, among students. Finally, mediation analyses indicated that the time spent in nature, social relationships, and levels of energy play a mediator role in the relationship between sport practice and SWB. Our evidence reinforces the protective role of time spent in nature in improving mental health, and provides support for policymakers to make appropriate choices for a better management of COVID-19 pandemic consequencesP.P. was funded by Life Quality Research Centre—UIDP/04748/2020, a program financially supported by FCT—Fundação para a Ciência e Tecnolo-gia/Ministério da Educação e Ciência.Peer reviewe

Extra virgin olive oil phenols down-regulate lipid synthesis in primarycultured rat- hepatocytes

Hydroxytyrosol, tyrosol, and oleuropein, the main phenols present in extra virgin olive oil, have been reported to exert several biochemical and pharmacological effects. Here, we investigated the short-term effects of these compounds on lipid synthesis in primary-cultured rat-liver cells. Hydroxytyrosol, tyrosol and oleuropein inhibited both de novo fatty acid and cholesterol syntheses without an effect on cell viability. The inhibitory effect of individual compounds was already evident within 2 h of 25 μM phenol addition to the hepatocytes. The degree of cholesterogenesis reduction was similar for all phenol treatments (-25/30%), while fatty acid synthesis showed the following order of inhibition: hydroxytyrosol (-49%) = oleuropein (-48%) > tyrosol (-30%). A phenol-induced reduction of triglyceride synthesis was also detected. To clarify the lipid-lowering mechanism of these compounds, their influence on the activity of key enzymes of fatty acid biosynthesis (acetyl-CoA carboxylase and fatty acid synthase), triglyceride synthesis (diacylglycerol acyltransferase) and cholesterogenesis (3-hydroxy-3-methyl-glutaryl-CoA reductase) was investigated in situ by using digitonin-permeabilized hepatocytes. Acetyl-CoA carboxylase, diacylglycerol acyltransferase and 3-hydroxy-3-methyl-glutaryl-CoA reductase activities were reduced after 2 h of 25 μM phenol treatment. No change in fatty acid synthase activity was observed. Acetyl-CoA carboxylase inhibition (hydroxytyrosol, -41%, = oleuropein, -38%, > tyrosol, -17%) appears to be mediated by phosphorylation of AMP-activated protein kinase. These findings suggest that a decrease in hepatic lipid synthesis may represent a potential mechanism underlying the reported hypolipidemic effect of phenols of extra virgin olive oil