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IntroductionIn our paper, we explored the impact of different anthropogenic stressors, namely, mussel farming, methane extraction platforms, and summer mass tourism, on the epipelagic microbiomes of the North-Western Adriatic Sea.MethodsBy 16S rRNA gene sequencing, we provided the epipelagic microbiome layout from selected sites corresponding to each of the considered impacts. As an unimpacted reference, we used already published 16S rRNA sequencing data.ResultsAccording to our findings, each one of the anthropogenic stressors resulted in a peculiar increase of specific epipelagic microbial components, including copiotrophic R-strategists and host-restricted bacteria, as well as some pathobiome components, the latter being detected exclusively in impacted sites. Particularly, potentially harmful pathogenic species such as Legionella impletisoli and Staphylococcus epidermidis have been detected in proximity to the mussel farms, and Escherichia coli and Campylobacter ureolyticus were present close to the methane extraction platform and at the summer mass tourism site, respectively. Particularly, C. ureolyticus is an emerging human gastrointestinal pathogen, capable of destroying intestinal microvilli.DiscussionIn addition to providing evidence supporting the existence of recognizable and impact-driven fingerprints on the epipelagic marine microbiome peculiar to the different anthropogenic stressors, our findings also raise concern about the ecological relevance of the observed changes, in terms of possible loss of ecosystem services and also for the potential release of pathogenic microorganisms in the environment.

Introduction: Detachment from the extracellular matrix (ECM) is the first step of the metastatic cascade. It is a regulated process involving interaction between tumor cells and tumor microenvironment (TME). Iron is a key micronutrient within the TME. Here, we explored the role of iron in the ability of ovarian cancer cells to successfully detach from the ECM.Methods: HEY and PEO1 ovarian cancer cells were grown in 3D conditions. To mimic an iron rich TME, culture media were supplemented with 100 μM Fe3+. Cell mortality was evaluated by cytofluorimetric assay. The invasive potential of tumor spheroids was performed in Matrigel and documented with images and time-lapses. Iron metabolism was assessed by analyzing the expression of CD71 and FtH1, and by quantifying the intracellular labile iron pool (LIP) through Calcein-AM cytofluorimetric assay. Ferroptosis was assessed by quantifying mitochondrial reactive oxygen species (ROS) and lipid peroxidation through MitoSOX and BODIPY-C11 cytofluorimetric assays, respectively. Ferroptosis markers GPX4 and VDAC2 were measured by Western blot. FtH1 knockdown was performed by using siRNA.Results: To generate spheroids, HEY and PEO1 cells prevent LIP accumulation by upregulating FtH1. 3D HEY moderately increases FtH1, and LIP is only slightly reduced. 3D PEO1upregulate FtH1 and LIP results significantly diminished. HEY tumor spheroids prevent iron import downregulating CD71, while PEO1 cells strongly enhance it. Intracellular ROS drop down during the 2D to 3D transition in both cell lines, but more significantly in PEO1 cells. Upon iron supplementation, PEO1 cells continue to enhance CD71 and FtH1 without accumulating the LIP and ROS and do not undergo ferroptosis. HEY, instead, accumulate LIP, undergo ferroptosis and attenuate their sphere-forming ability and invasiveness. FtH1 knockdown significantly reduces the generation of PEO1 tumor spheroids, although without sensitizing them to ferroptosis.Discussion: Iron metabolism reprogramming is a key event in the tumor spheroid generation of ovarian cancer cells. An iron-rich environment impairs the sphere-forming ability and causes cell death only in ferroptosis sensitive cells. A better understanding of ferroptosis sensitivity could be useful to develop effective treatments to kill ECM-detached ovarian cancer cells.

In response to the accidental exhumation of three ancient trees by farmers, we conducted a multidisciplinary study based on the stratigraphic analysis of boreholes, carbon-14 dating, aerial photo interpretation, and analysis of palaeobotanical and archaeological evidences. We reconstructed the formation and evolution during Roman times of a first “continuous” and then “discontinuous” deltaic strandplain at the mouth of the Carapelle Stream in the Tavoliere di Puglia Plain—the second-largest plain in Italy. Ttwo main phases can be recognised in the evolution of the Carapelle deltaic strandplain: 1) a first phase, lasted until ca. the birth of Christ, was characterised by a regular and continuous construction of sand ridges one leaning against the other; 2) a second phase, lasted more or less from the birth of Christ to the termination of the construction of the deltaic strandplain, was characterised by the discontinuous construction of sand ridges/coastal barriers with the isolation of lagoons/ponds, and by evidences of alluvial events. The most probable climatic–environmental scenario to have formed the Roman-period deltaic strandplain implied that: 1) the first phase was triggered by a higher total amount of precipitations, but with less extreme alluvial events; 2) the second phase was triggered by a total amount of precipitation lower than the previous period, but with higher occurrence of extreme alluvial events and/or by extreme alluvial events separated by longer period of low precipitations. This second phase was enhanced by the opening of vegetation. The passage between the first and second phase of the Carapelle deltaic strandplain coincides with the passage from overall negative NAO index to an overall positive NAO index.

IntroductionWines produced from the same grape cultivars but in different locations possess distinctive qualities leading to different consumer’s appreciation, preferences, and thus purchase choices. Here, we explore the possible importance of microbiomes at the soil–plant interface as a determinant of the terroir properties in grapevine production, which confer specific growth performances and wine chemo-sensory properties at the local scale.MethodsIn particular, we investigated the variation in microbial communities associated with the roots of Vitis vinifera cultivar Lambrusco, as well as with surrounding bulk soils, in different vineyards across the “Consorzio Tutela Lambrusco DOC” protected designation of origin area (PDO, Emilia Romagna, Italy), considering viticultural sites located both inside and outside the consortium in two different seasons (June and November 2021).ResultsAccording to our findings, rhizospheric and soil microbiomes show significant structural differences in relation to the sampling site, regardless of seasonality, while endophytic microbiomes seem to be completely unaffected by such variables. Furthermore, a deeper insight into the microbial terroir of PDO areas highlighted the presence of some rhizospheric microorganisms enriched inside the consortium and characterizing the PDO regardless of both sampling season and farming strategy. These include Bacillus, Paenibacillus, and Azospirillum, which are all well-known plant growth-promoting bacteria.DiscussionTaken together, our results suggest a connection between soil and root microbiomes of V. vinifera cultivar Lambrusco and the local designation of origin, emphasizing the potential role of PDO-enriched plant growth-promoting bacteria in vine growing and final quality of the Lambrusco DOC wine.

BackgroundEven in the early stages, global crises such as the COVID-19 pandemic lead to serious dislocations of social life, secondary adjustment reactions to external restrictions and individual concerns. Coping mechanisms may also include dysfunctional strategies like an increase of drug use. Considering the wide-spread use of cannabis, the aim of this study was to elucidate the interplay of social restrictions, psychopathology, concerns related to the pandemic in addition to the users’ experiences, motivations and consumption quantities during the early COVID-19 pandemic. It was presumed that cannabis intake would increase during the early phase of the crisis and that consumption quantities would be related to corona-related restrictions, concerns as well as subjective substance effects and psychopathology.Materials and methodsAs part of an international, cross-sectional, internet-based survey (N = 5,049) available in five languages, consumption quantities and patterns of cannabis use in the early phase of the pandemic from April to August 2020 were examined. Participants retrospectively rated restrictions and concerns related to the pandemic, motives of cannabis use prior to and during 1 month the pandemic, and subjective consumption effects.ResultsCannabis use behavior showed no significant differences when consumption quantities prior and during 1 month after the COVID-19 outbreak were compared. Higher quantities of cannabis intake prior and during 1 month of the pandemic as well as more corona-related concern were associated with an increased perception of positive effects of cannabis during the pandemic. Predictors of its use during 1 month of pandemic were higher pre-pandemic consumption quantity, older age, quarantinization, a lesser degree of being affected by negative effects of the pandemic and a stronger subjective experience of corona-related positive effects of cannabis. Comparisons of the motives for cannabis intake in the pre-pandemic versus the pandemic period showed that all rationales for consumption were reported less frequently, except boredom.ConclusionFrequencies of cannabis intake remained relatively stable in the early pandemic phase. Risk factors for increased use seem related to habitual consumption patterns that become more prominent under quarantinization. The use of cannabis as a dysfunctional coping strategy might not be amenable via self-report and should therefore receive special attention in clinical contexts.

Background: The aim of the study was to evaluate the efficacy and safety of direct oral anticoagulants (DOACs) in a subgroup of patients with atrial fibrillation (AF), CHADS2 score ≥3, advanced age, and heart failure (HF) coming from the main DOACs randomized clinical trials.Methods: We searched MEDLINE, MEDLINE In-Process, and Other Non-Indexed Citations, EMBASE, PubMed, and the Cochrane Central Register of Controlled Trials. English-language articles published from 2002 to March 2019 dealing with DOACs for preventing thrombotic events in AF were considered. We did not conduct any statistical analyses, as indirect comparison between DOACs represents hypothesis generators.Results: This systematic review was restricted to the subgroup of patients with CHADS2 score ≥3 (n = 31,203), elderly (n = 24,788), and with HF (n = 29,297) derived from the pivotal trials. Risk index (RI) was calculated. The RI for stroke/systemic embolism was similar in all of the patients treated with DOACs or warfarin. The lowest RI was in rivaroxaban patients (CHADS2 score ≥3: RI = 0.04; elderly: RI = 0.09; HF: RI = 0.05). The RIs for bleeding were higher in patients treated with dabigatran (CHADS2 score ≥3: RI110 = 0.23; elderly: RI110 = 0.22; HF: RI110 = 0.16; CHADS2score ≥3: RI150 = 0.30; elderly: RI150 = 0.24; HF: RI150 = 0.16). The bleeding RIs were higher with apixaban (CHADS2 score ≥3: RI = 0.23; elderly: RI = 0.25; HF: RI = 0.14) and dabigatran (CHADS2 score ≥3: RI = 0.28; elderly: RI = 0.21; HF: RI = 0.19).Conclusions: The use of DOACs is a reasonable alternative to vitamin K antagonists in AF patients with CHADS2 score ≥3, advanced age, and HF. The RI constitutes a useful, additional tool to facilitate clinicians in choosing DOACs or warfarin in particular category of AF patients.

Preventive therapy can target hormone-responsive breast cancer (BC) by treatment with selective estrogen receptor modulators (SERMs) and reduce the incidence of BC. Genome-wide association studies have identified single nucleotide polymorphisms (SNPs) with relevant predictive values, SNPs in the ZNF423 gene were associated with decreased risk of BC during SERM therapy, and SNPs in the Cathepsin O gene with an increased risk. ZNF423, which was not previously associated with BC is a multifunctional transcription factor known to have a role in development, neurogenesis, and adipogenesis and is implicated in other types of cancer. ZNF423 is transcriptionally controlled by the homolog ZNF521, early B cell factor transcription factor, epigenetic silencing of the promoter by CpG island hyper-methylation, and also by ZNF423 itself in an auto-regulatory loop. In BC cells, ZNF423 expression is found to be induced by estrogen, dependent on the binding of the estrogen receptor and calmodulin-like 3 to SNPs in ZNP423 intronic sites in proximity to consensus estrogen response elements. ZNF423 has also been shown to play a mechanistic role by trans-activating the tumor suppressor BRCA1 and thus modulating the DNA damage response. Even though recent extensive trial studies did not classify these SNPs with the highest predictive values, for inclusion in polygenic SNP analysis, the mechanism unveiled in these studies has introduced ZNF423 as a factor important in the control of the estrogen response. Here, we aim at providing an overview of ZNF423 expression and functional role in human malignancies, with a specific focus on its implication in hormone-responsive BC.

Despite their recognized primary importance, marine coastal ecosystems around the globe are currently under threat, being subject to continuous local and global anthropogenic stressors. In this frame, understanding the response of coastal habitat-forming species to multiple stressors and their resilience is fundamental for the sustainable management of coastal ecosystems. In the present study, to provide some glimpses in this direction, we explored the response of the Anemonia viridis-associated microbiota to the combined anthropogenic stressors, which typically affect touristic hotspots at Mediterranean coastal sites. To this aim, two case studies have been carried out, the first in the Riccione coastal site (Italy, Center Mediterranean) and the second at Cap de Creus (Spain, North-western Mediterranean), where the A. viridis microbiota was assessed under the conditions of both high and low anthropogenic pressure. According to our findings, the A. viridis microbiota showed a relevant degree of plasticity in response to combined anthropogenic and environmental stressors, with changes that also mirrored variations in the surrounding seawater, thus indicating a close connection with the environment, from which potential symbiotic partners are selected. However, this potentially adaptive process also has a limitation, as observed in the highly anthropogenic impact site of Cap de Creus, where A. viridis-associated microbiota appeared completely unstructured, as demonstrated by an increased dispersion according to the Anna Karenina principle. This raises the question about the resilience of the A. viridis-associated microbiota under combined climate and anthropogenic threats, as well as of the anthropogenic factors driving the observed dysbiosis changes.

In this study, we report on the results of SARS-CoV-2 surveillance performed in an area of Southern Italy for 12 months (from March 2021 to February 2022). To this study, we have sequenced RNA from 609 isolates. We have identified circulating VOCs by Sanger sequencing of the S gene and defined their genotypes by whole-genome NGS sequencing of 157 representative isolates. Our results indicated that B.1 and Alpha were the only circulating lineages in Calabria in March 2021; while Alpha remained the most common variant between April 2021 and May 2021 (90 and 73%, respectively), we observed a concomitant decrease in B.1 cases and appearance of Gamma cases (6 and 21%, respectively); C.36.3 and Delta appeared in June 2021 (6 and 3%, respectively); Delta became dominant in July 2021 while Alpha continued to reduce (46 and 48%, respectively). In August 2021, Delta became the only circulating variant until the end of December 2021. As of January 2022, Omicron emerged and took over Delta (72 and 28%, respectively). No patient carrying Beta, Iota, Mu, or Eta variants was identified in this survey. Among the genomes identified in this study, some were distributed all over Europe (B1_S477N, Alpha_L5F, Delta_T95, Delta_G181V, and Delta_A222V), some were distributed in the majority of Italian regions (B1_S477N, B1_Q675H, Delta_T95I and Delta_A222V), and some were present mainly in Calabria (B1_S477N_T29I, B1_S477N_T29I_E484Q, Alpha_A67S, Alpha_A701S, and Alpha_T724I). Prediction analysis of the effects of mutations on the immune response (i.e., binding to class I MHC and/or recognition of T cells) indicated that T29I in B.1 variant; A701S in Alpha variant; and T19R in Delta variant were predicted to impair binding to class I MHC whereas the mutations A67S identified in Alpha; E484K identified in Gamma; and E156G and ΔF157/R158 identified in Delta were predicted to impair recognition by T cells. In conclusion, we report on the results of SARS-CoV-2 surveillance in Regione Calabria in the period between March 2021 and February 2022, identified variants that were enriched mainly in Calabria, and predicted the effects of identified mutations on host immune response.

Introduction: The current corona virus disease (COVID-19) pandemic has caused a serious global health crisis that has affected large parts of the public and private life worldwide, including the use of psychoactive substances. In this study, we investigated the effect of the COVID-19 pandemic on the use of serotonergic psychedelics, i.e., the settings in which people use psychedelics, the motives of usage, and the subjective quality of psychedelic experiences.Methods: The study was part of an international, cross-sectional, internet-based survey (N = 5,049) available in five languages (English, German, Spanish, Italian, and Korean) carried out during the early phase of the pandemic from April to August 2020. Participants were asked to retrospectively rate settings and motives of psychedelic substance use before the pandemic and in the last 4 weeks during the pandemic, as well as changes in psychedelic experiences.Results: Of n = 1,375 participants that reported the use psychedelics in 2019 or 2020, n = 642 (46.6%) also took psychedelics during the pandemic. During the pandemic, participants used psychedelics significantly less often in settings that were outside their home. Top motives to use psychedelics were comparable before and during the pandemic, but participants consumed less out of curiosity, to celebrate, or because friends took it, and more out of boredom. An increase in positively connoted, often pro-social experiences was observed. Two thirds of participants who used psychedelics during the pandemic claimed that psychedelics had helped them to deal better with the corona pandemic at least slightly.Discussion: Changes in setting and motives were mostly in line with restrictions caused by control measures to contain the spread of the virus. The unexpected increase in positively connoted experiences possibly reflects a favorable interaction of environmental macro- and individual micro-contexts during the pandemic (e.g., by reducing the use in more uncontrolled recreational settings or by encouraging a strong self-selection of substance users due to the expectation of “bad trips”). Increased pro-social feelings under psychedelics might reflect a desire for social interactions in times of social distancing and pandemic-related stress and anxiety.

Background: The COVID-19 pandemic may lead to negative mental health effects but the effect on alcohol consumption among younger adults is unclear. We assess predictors of change in alcohol consumption during the first phase of the COVID-19 pandemic among younger adults.Methods: This cross-sectional internet-based survey was part of an overarching project, the Corona Drug Survey, which was conducted from April 30 to August 4, 2020. Participants of any sex and ≥18 years old were included. The primary outcome measure was change in alcohol consumption during the early COVID-19 pandemic. We implemented an ordinal logistic regression to assess the effect (odds ratio [OR] and 95% confidence interval [CI]) of the following predictors: quarantine restrictions on leaving the residence, number of individuals in the household, problematic alcohol consumption before the pandemic (CAGE [cutting down, annoyance by criticism, guilty feeling, and eye-opener] score), personal concern regarding the pandemic, age, and sex.Results: 3,321 participants with a mean age of 32 (SD: 13) years were included in this study. 70.4% of participants reported less or unchanged alcohol consumption in the recent 4 weeks of the pandemic compared to before the pandemic. A higher number of individuals in the household was associated with a reduced alcohol consumption (OR = 0.869; 95% CI = 0.815–0.927). No quarantine restrictions on leaving the residence (OR = 1.593; 95% CI = 1.397–1.817), a higher age (1.006; 1.001-1.011), and female sex (compared to males: 1.206; 1.062–1.371) were associated with an increase in alcohol consumption. The CAGE score before the pandemic (OR = 0.983; 95% CI = 0.931–1.037) and the pandemic concern (0.927; 0.857–1.003) were not associated with a significant change in alcohol consumption. Celebrations were no longer frequent drinking occasions during the pandemic compared to before the pandemic. The majority of participants (60.9%) did not use alcohol drinking as a coping mechanism to mitigate negative effects of the pandemic.Interpretation: In this cohort of younger adults with fewer celebratory drinking occasions, restrictions on leaving the residence and the number of persons in the household were the strongest predictors of reduced alcohol consumption during the early phase of the pandemic.

A 121-day feeding trial was undertaken to test the effects of two dietary lipid levels (16 and 21% L16, L21) in triplicated gilthead sea bream groups (initial weight: 67.5 g) reared at two different water temperatures (high, H 23°C and low, L 17°C) in the same recirculation system but exposed to a switch in temperature after 58 days. Fish kept at H were transferred to L (HL transition, autumn shift), and the fish kept at L were exposed to H (LH transition, summer shift), while continuing to receive the same diet to apparent satiation in each group. At the end of the trial, no significant diet effect on specific growth rate (SGR), feed intake (FI), and feed conversion rate (FCR) were detected in fish exposed to HL transition compared with those exposed to LH transition, while gross lipid efficiency (GLE) and lipid efficiency ratio (LER) were higher in L16. After temperature changes, L16 displayed higher SGR, FI, GLE, and LER, while mesenteric fat index was reduced. After temperature changes, the combined effects of low lipid diet and low temperature conditions resulted in higher pepsin activity, while trypsin, chymotrypsin, and lipase activities were generally higher at high lipid content. The combined effect of diet and temperature did not alter the metabolic plasma profile, except for the observed final higher aspartate aminotransferase (AST) and alkaline phosphatase (ALP) values when combining high dietary lipid (L21) and temperature changes. Different diets showed a significantly different gut microbiome layout, only at high temperature with L16 diet resulting in a higher load of Lactobacillus. On the contrary, no dietary impact on ecosystem diversity was observed, independently from the temperature. In addition, L16 diet in the HL transition favored an increase in Weissella and Bradyrhizobium genera in the gut microbiome, while in the final condition of LH transition, L21 diet favored a significant increase in Streptococcus and Bacillus. According to the results, the utilization of 16% dietary lipid levels in gilthead sea bream should be preferred during seasonal temperature changes in order to optimize feed utilization and gut health.

Metabolic syndrome is not a single pathology, but a constellation of cardiovascular disease risk factors including: central and abdominal obesity, systemic hypertension, insulin resistance (or type 2 diabetes mellitus), and atherogenic dyslipidemia. The global incidence of Metabolic syndrome is estimated to be about one quarter of the world population; for this reason, it would be desirable to better understand the underlying mechanisms involved in order to develop treatments that can reduce or eliminate the damage caused. The effects of Metabolic syndrome are multiple and wide ranging; some of which have an impact on the central nervous system and cause neurological and neurodegenerative diseases. Autophagy is a catabolic intracellular process, essential for the recycling of cytoplasmic materials and for the degradation of damaged cellular organelle. Therefore, autophagy is primarily a cytoprotective mechanism; even if excessive cellular degradation can be detrimental. To date, it is known that systemic autophagic insufficiency is able to cause metabolic balance deterioration and facilitate the onset of metabolic syndrome. This review aims to highlight the current state of knowledge regarding the connection between metabolic syndrome and the onset of several neurological diseases related to it. Furthermore, since autophagy has been found to be of particular importance in metabolic disorders, the probable involvement of this degradative process is assumed to be responsible for the attenuation of neurological disorders resulting from metabolic syndrome.

Different bacterial families colonize most mucosal tissues in the human organism such as the skin, mouth, vagina, respiratory, and gastrointestinal districts. In particular, the mammalian intestine hosts a microbial community of between 1,000 and 1,500 bacterial species, collectively called “microbiota.” Co-metabolism between the microbiota and the host system is generated and the symbiotic relationship is mutually beneficial. The balance that is achieved between the microbiota and the host organism is fundamental to the organization of the immune system. Scientific studies have highlighted a direct correlation between the intestinal microbiota and the brain, establishing the existence of the gut microbiota–brain axis. Based on this theory, the microbiota acts on the development, physiology, and cognitive functions of the brain, although the mechanisms involved have not yet been fully interpreted. Similarly, a close relationship between alteration of the intestinal microbiota and the onset of several neurological pathologies has been highlighted. This review aims to point out current knowledge as can be found in literature regarding the connection between intestinal dysbiosis and the onset of particular neurological pathologies such as anxiety and depression, autism spectrum disorder, and multiple sclerosis. These disorders have always been considered to be a consequence of neuronal alteration, but in this review, we hypothesize that these alterations may be non-neuronal in origin, and consider the idea that the composition of the microbiota could be directly involved. In this direction, the following two key points will be highlighted: (1) the direct cross-talk that comes about between neurons and gut microbiota, and (2) the degree of impact of the microbiota on the brain. Could we consider the microbiota a valuable target for reducing or modulating the incidence of certain neurological diseases?

Plastic pollution is nowadays a relevant threat for the ecological balance in marine ecosystems. Small plastic debris (PD) can enter food webs through various marine organisms, with possible consequences on their physiology and health. The loggerhead sea turtle (Caretta caretta), widespread across the whole Mediterranean Sea, is a “flagship species,” useful as indicator of the general pollution level of marine ecosystems. Ingested PD accumulate in the final section of turtles’ digestive tract before excretion. During their transit and accumulation, PD also interact with the residing microbial community, with possible feedback consequences on the host’s health. To explore the possible relationship between fecal microbial composition and PD ingestion, we collected fecal samples from 45 turtles rescued between 2017 and 2019 in the Northwestern Adriatic Sea (Italy), assessing occurrence and content of PD in the samples and in parallel the microbiome structure by 16S rRNA gene sequencing. According to our findings, almost all samples contained PD, mirroring the high level of plastic pollution in the area. We identified phylotypes associated to a high amount of PD, namely Cetobacterium somerae and other taxa, possibly responding to contamination by plastic-associated chemicals. Furthermore, putative marine pathogens were found associated to higher plastic contamination, supporting the hypothesis that PD can act as a carrier for environmental pathogenic bacteria into marine organisms. Besides confirming the role of the sea turtle as relevant flagship species for plastic pollution of the marine environment, our study paves the way to the exploration of the impact that PD ingestion can have on the microbial counterpart of large marine organisms, with potential feedback consequences on the animal and ecosystem health.

Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disorder, classified into sporadic or familial forms and characterized by motor neurons death, muscle atrophy, weakness, and paralysis. Among the familial cases of ALS, approximately 20% are caused by dominant mutations in the gene coding for superoxide dismutase (SOD1) protein. Of note, mutant SOD1 toxicity is not necessarily limited to the central nervous system. ALS is indeed a multi-systemic and multifactorial disease that affects whole body physiology and induces severe metabolic changes in several tissues, including skeletal muscle. Nevertheless, whether alterations in the plasticity, heterogeneity, and metabolism of muscle fibers are the result of motor neuron degeneration or alternatively occur independently of it remain to be elucidated. To address this issue, we made use of a mouse model (MLC/SOD1G93A) that overexpresses the SOD1 mutant gene selectively in skeletal muscle. We found an alteration in the metabolic properties of skeletal muscle characterized by alteration in fiber type composition and metabolism. Indeed, we observed an alteration of muscle glucose metabolism associated with the induction of Phosphofructokinases and Pyruvate dehydrogenase kinase 4 expression. The upregulation of Pyruvate dehydrogenase kinase 4 led to the inhibition of Pyruvate conversion into Acetyl-CoA. Moreover, we demonstrated that the MLC/SOD1G93A transgene was associated with an increase of lipid catabolism and with the inhibition of fat deposition inside muscle fibers. All together these data demonstrate that muscle expression of the SOD1G93A gene induces metabolic changes, along with a preferential use of lipid energy fuel by muscle fibers. We provided evidences that muscle metabolic alterations occurred before disease symptoms and independently of motor neuron degeneration, indicating that skeletal muscle is likely an important therapeutic target in ALS.