Quercetin Reduces Lipid Accumulation in a Cell Model of NAFLD by Inhibiting De Novo Fatty Acid Synthesis through the Acetyl‐CoA Carboxylase 1/AMPK/PP2A Axis

none6noDysregulation of de novo lipogenesis (DNL) has recently gained strong attention as being one of the critical factors that contribute to the assessment of non‐alcoholic fatty liver disease (NAFLD). NAFLD is often diagnosed in patients with dyslipidemias and type 2 diabetes; thus, an interesting correlation can be deduced between high hematic free fatty acids and glucose excess in the DNL dysregulation. In the present study, we report that, in a cellular model of NAFLD, the coexistence of elevated glucose and FFA conditions caused the highest cellular lipid accumulation. Deepening the molecular mechanisms of the DNL dysregulation—RT‐qPCR and immunoblot analysis demonstrated increased expression of mitochondrial citrate carrier (CiC), cytosolic acetyl‐ CoA carboxylase 1 (ACACA), and diacylglycerol acyltransferase 2 (DGAT2) involved in fatty acids and triglycerides synthesis, respectively. XBP‐1, an endoplasmic reticulum stress marker, and SREBP‐1 were the transcription factors connected to the DNL activation. Quercetin (Que), a flavonoid with strong antioxidant properties, and noticeably reduced the lipid accumulation and the expression of SREBP‐1 and XBP‐1, as well as of their lipogenic gene targets in steatotic cells. The anti‐lipogenic action of Que mainly occurs through a strong phosphorylation of ACACA, which catalyzes the committing step in the DNL pathway. The high level of ACACA phosphorylation in Que‐treated cells was explained by the intervention of AMPK together with the reduction of enzymatic activity of PP2A phosphatase. Overall, our findings highlight a direct anti‐lipogenic effect of Que exerted through inhibition of the DNL pathway by acting on ACACA/AMPK/PP2A axis; thus, suggesting this flavonoid as a promising molecule for the NAFLD treatment.openGnoni A.; Di Chiara Stanca B.; Giannotti L.; Gnoni G.V.; Siculella L.; Damiano F.Gnoni, A.; Di Chiara Stanca, B.; Giannotti, L.; Gnoni, G. V.; Siculella, L.; Damiano, F

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

Effect of starvation on the activity of the mitochondrial tricarboxylate carrier

AbstractThe effect of starvation on the activity of the tricarboxylate carrier has been investigated in intact rat liver mitochondria and in a reconstituted system. In both experimental conditions, the rate of citrate transport, when compared to control, is greatly reduced (35–40%) in starved rats. Similar behaviour is shown by the cytosolic lipogenic enzymes. Kinetic analysis of the carrier activity in intact mitochondria and in the proteoliposomal system has showed that during starvation only the Vmax of this process decreases while there is no change in the Km. No difference in the Arrhenius plot and in the lipid composition has been detected, which indicates that the reduced transport activity in fasted animals is not due to a change in the carrier lipid microenvironment. In starved rats, a reduction of the carrier activity has occurred even after the addition of increasing cardiolipin concentrations to proteoliposomes. These findings thus suggest that starvation-induced decrease of citrate carrier activity could be due to a change of the intrinsic properties of the transport protein

E-waste Management as a Global Challenge (Introductory Chapter)

Waste Electrical and Electronic Equipment management (E-waste or WEEE) is a crucial issue in the solid waste management sector with global interconnections between well-developed, transitional and developing countries. Consumption society and addiction to technology dictate the daily life in high and middle-income countries where population consumes large amounts of EEE products (electrical and electronic equipment) which sooner become e-waste. This fraction is a fast-growing waste stream which needs special treatment and management due to the toxic potential of public health and environment. On the other hand, the e-waste contains valuable materials which may be recovered (precious metals, Cu) reused and recycled (metals, plastics) by various industries mitigating the consumption of natural resources. The new challenge of e-waste management system is to shift the paradigm from a toxic pollution source to a viable resource in the context of sustainable development

Is there any role of intermittent fasting in the prevention and improving clinical outcomes of COVID-19?: intersection between inflammation, mTOR pathway, autophagy and calorie restriction

The coronavirus disease 2019 (COVID-19) pandemic is provoking a global public health crisis. Even though the academic world is intensively pursuing new therapies, there is still no “game changer” in the management of COVID 19. The Mammalian Target of Rapamycin (mTOR) is an ancient signaling system that has been proposed as a molecular tool used by coronaviruses and other RNA and DNA viruses in order to replicate and persist in the host cell. In recent years, Intermittent Fasting (IF), a practice consisting on a strict calorie restriction during a prolonged period of time during the day, has gained popularity due to its potential benefits in multiple health systems and in regulating inflammation. IF inhibits the mTOR pathway which is similar to the effects of Rapamycin in some animal models. mTOR inhibition and promotion of autophagy could potentially be the link between the possible direct benefits of IF in COVID-19 due to the interruption of the viral cycle (protein synthesis). Besides, IF has shown to be a strong anti-inflammatory in multiple prior studies, and may play a role in attenuating COVID -19 severity. This review hypothesizes the possible intersection between viral, immunological, and metabolic pathways related to mTOR and the potential mechanisms through which IF may improve clinical outcomes. Future prospective randomized controlled clinical trials to evaluate intermittent fasting (IF) regimens in order to prevent and treat moderate to severe forms of COVID-19 in humans are needed.Revisión por pare

Possible Role of Tetracyclines on COVID-19: Recycling Well-Known Old Drugs from the Shelf

We are in the midst of a pandemic due to the novel coronavirus SARS-CoV-2. Innovative therapies are in the lookup around the world. Recently, chloroquine and hydroxychloroquine in addition to Azithromycin were proposed to be used in patients with severe disease even though strong evidence is lacking. We propose the use of tetracyclines in addition to anti-virals early in the curse of the disease in order to prevent the Cytokine Storm Syndrome associated with COVID-19 and prevent ARDS. The proposed mechanisms of tetracyclines are: 1) anti-apoptotic properties; 2) decrease the Myeloperoxidase and ROS releaser from immune cells; 3) decrease neutrophil and monocyte migration and chemotaxis; 4) decrease the secretion of pro-inflammatory and vasoactive cytokines from macrophages (IL-1 beta, IL-8, and TNF-alpha); 5) inhibition of iNOS expression; 6) inhibition of chemotaxis of peripheral monocytes; 7) inhibition of IL-6 production and its receptor system; 8) prevention of fibrosis; and 9) inhibition of metalloproteinases (particularly MMP-2 and 9). Tetracyclines are well-known drugs with lower costs, and are not associated with adverse effects like QT prolongation. Clinical trials are needed to test our hypothesis

Assessing the Efficiency of a PSS Solution for Waste Collection: A Simulation Based Approach ☆

Abstract Driven by both policy pressures and environmental concerns, new business models are becoming applied in waste management mainly based on introducing more equitable and sustainable pricing schemes (e.g. "pay-as-you-throw"): the aim is to support the transition from a tax based system to a pure service based approach, where the user pays for the actual use of the waste management service provided. This new trend requires the service provider's activities to be planned with a schedule that reflects the actual users' needs in order to reach a real efficiency in the collection phase: dynamic routing and scheduling schemes, which could be enabled through the application of smart technologies, can lead to a more rational use of the resources. In the last decade, technological progresses allowed a growing use of IoT (Internet-of-Things) applications in the service sector; recent pilot applications are being tested also in waste management; one example is the introduction of bin level detection and data transmission technologies for waste collection. This work aims to contribute to the assessment of IoT-based PSS solutions for waste collection. The main objective is to evaluate the cost efficiency of a PSS for waste collection enabling dynamic scheduling, comparing it to the performance of more common schemes (e.g. fixed routing and scheduling service and call-based service). Hybrid simulation modelling – based on system dynamics, discrete events and agent based modelling- has been applied to test the transition from a fixed to a "pay-as-you-throw" fee in WEEE (waste from electrical and electronic equipment). A test case regarding an Italian municipality has been proposed to assess quantitative results based on a simulation model