A Novel Synthesized Cyclohexane-Hydroxytyrosol Derivative Suppresses Ovarian Cancer Cell Growth Through Inducing Reactive Oxidative Species and Blocking Autophagic Flux.

Aims: Drug resistance in ovarian cancer (OC) cells often leads to recurrence, metastasis, and high mortality rates among OC patients. Hydroxytyrosol (HT) has been reported to inhibit the proliferation of ovarian and other types of cancer cells. Here we synthesized a novel cyclohexane-hydroxytyrosol derivative (Chx-HT) for enhanced anticaner efficacy. We examined the growth-suppressing effect of Chx-HT on OC cells in vitro and in a xenograft mouse model and investigated the underlying mechanism. Results: We demonstrated that Chx-HT inhibits proliferation, promotes apoptosis, and remodels glucose and lipid metabolism by reducing fatty acid ß-oxidation while increasing glycolysis, de novo fatty acid synthesis (FAS), and lipid droplet (LD) accumulation, impairs mitochondrial respiration, and induces oxidative stress both in vitro and in vivo. In addition, Chx-HT blocks autophagic flux by obstructing the maturation of lysosomal cathepsins in the late stage, but also activates autophagy through the p-AMPK/p-mTOR/p-ULK1 pathway in response to energy deficit. Innovation and Conclusion: Reactive oxidative species (ROS) play a critical role in mediating the effects of Chx-HT on proliferation, apoptosis, autophagy, tricarboxylic acid (TCA) cycle, fatty acid ß-oxidation, and mitochondrial respiration, and the autophagic activation underlies the effects of Chx-HT on glycolysis, de novo FAS, and LD accumulation in OC cells. Cotreating OC cells with Chx-HT and autophagic inhibitor or glycolytic inhibitor results in an additive inhibition of proliferation. Our study indicates that Chx-HT stands for a promising OC therapeutic by ROS and autophagy blockade-mediated metabolic remodeling.

The causal relationship between psoriasis and chronic obstructive pulmonary disease: A bidirectional mendelian randomization study.

PURPOSE: Although many studies have investigated the association between psoriasis and chronic obstructive pulmonary disease (COPD), the causal relationship between psoriasis and COPD is still unknown. METHODS: We employed bidirectional Mendelian randomization to investigate the causal relationship between psoriasis and COPD. Genetic instruments for exposure were selected from two distinct genome-wide association study databases. Single nucleotide polymorphisms associated with exposures at the genome-wide significance level (p < 5 × 10^-8 ) and exhibiting low linkage disequilibrium (r^2  < 0.001) were chosen as instrumental variables. Causality was assessed using multiple MR methods, including Inverse-Variance Weighted (IVW), MR-Egger, Weighted Median, Simple Mode, and Weighted Mode. A significance level of p < 0.05 was considered statistically significant. Heterogeneity was examined using Cochran's Q test, and MR-Egger regression was employed to detect pleiotropy. The robustness and reliability of the results were further evaluated through leave-one-out analysis. RESULTS: We found a positive causal association between psoriasis and COPD [IVW: odds ratio (OR): 1.0006; p = 0.0056]. Heterogeneity and pleiotropy have not been discovered, so the results of the study are reliable. In the reverse analysis, no causal association between CPOD and psoriasis was found. CONCLUSION: Our findings revealed that psoriasis was associated with an elevated risk of COPD. However, no causal association between COPD and psoriasis was identified in our study.

The impact of social hierarchies on neural response to feedback evaluations after advice giving.

Advisors generally evaluate advisee-relevant feedback after advice giving. The response to these feedback-(1) whether the advice is accepted and (2) whether the advice is optimal-usually involves prestige. Prior literature has found that prestige is the basis by which individuals attain a superior status in the social hierarchy. However, whether advisors are motivated to attain a superior status when engaging in advice giving remains uncharacterized. Using event-related potentials, this study investigates how advisors evaluate feedback after giving advice to superior (vs. inferior) status advisees. A social hierarchy was first established based on two advisees (one was ranked as superior status and another as inferior status) as well as participants' performance in a dot-estimation task in which all participants were ranked as medium status. Participants then engaged in a game in which they were assigned roles as advisors to a superior or inferior status advisee. Afterward, the participants received feedback in two phases. In Phase 1, participants were told whether the advisees accepted the advice provided. In Phase 2, the participants were informed whether the advice they provided was correct. In these two phases, when the advisee was of superior status, participants exhibited stronger feedback-related negativity and P300 difference in response to (1) whether their advice was accepted, and (2) whether their advice was correct. Moreover, the P300 was notably larger when the participants' correct advice led to a gain for a superior-status advisee. In the context of advice giving, advisors are particularly motivated to attain a superior status when the feedback involving social hierarchies, which is reflected in higher sensitivity to feedback associated with superior status advisees at earlier and later stages during feedback evaluations in brains.

Nuclear Factor Erythroid 2 Related Factor 2 and Mitochondria Form a Mutually Regulating Circuit in the Prevention and Treatment of Metabolic Syndrome.

Significance: Metabolic syndrome (MetS) has become a major global public health problem and there is an urgent need to elucidate its pathogenesis and find more effective targets and modalities for intervention. Recent Advances: Oxidative stress and inflammation are two of the major causes of MetS-related symptoms such as insulin resistance and obesity. Nuclear factor erythroid 2 related factor 2 (Nrf2) is one of the important systems responding to oxidative stress and inflammation. As cells undergo stress, cysteines within Kelch-like ECH-associated protein 1 (Keap1) are oxidized or electrophilically modified, allowing Nrf2 to escape ubiquitination and be translocated from the cytoplasm to the nucleus, facilitating the initiation of the antioxidant transcriptional program. Meanwhile, a growing body of evidence points out a specific modulation of mitochondrial homeostasis by Nrf2. After nuclear translocation, Nrf2 activates downstream genes involved in various aspects of mitochondrial homeostasis, including mitochondrial biogenesis and dynamics, mitophagy, aerobic respiration, and energy metabolism. In turn, mitochondria reciprocally activate Nrf2 by releasing reactive oxygen species and regulating antioxidant enzymes. Critical Issues: In this review, we first summarize the interactions between Nrf2 and mitochondria in the modulation of oxidative stress and inflammation to ameliorate MetS, then propose that Nrf2 and mitochondria form a mutually regulating circuit critical to maintaining homeostasis during MetS. Future Directions: Targeting the Nrf2-mitochondrial circuit may be a promising strategy to ameliorate MetS, such as obesity, diabetes, and cardiovascular diseases.

The Influence of Green Product Type, Message Framing, and Anticipated Pride on Green Consumption Behavior: An Event-Related Potential (ERP) Study.

Different types of green products require different marketing approaches to promote individual green purchasing behaviors. Previous studies have focused only on the effects of message framing on the promotion of different types of green products; however, little is known about the role of underlying emotions. Using event-related potentials (ERPs), this study investigated the neural responses to message framings and anticipated pride in green product types to assess their level of influence on green consumption. Participants in this study were randomly assigned to the anticipated pride versus control groups, and asked to make green consumption decisions involving different types (self- vs. other-interested) of green products, utilizing both gain and loss framing. The behavioral results demonstrated that participants in the anticipated pride group made more green product purchase choices than those in the control group. The ERP results showed that within the loss framing of the control group, other-interested green products induced larger N400 and smaller late positive potential (LPP) amplitudes than self-interested green products, whereas the results showed the opposite trend for the anticipated pride group. These results indicate that although individuals might have biases in their motivation that lead them to focus on self-interested green products, anticipating pride reduces cognitive conflicts and increases their motivation to focus on other-interested green products in the context of loss.

4EBP2-regulated protein translation has a critical role in high-fat diet-induced insulin resistance in hepatocytes.

A high-fat diet (HFD) plays a critical role in hepatocyte insulin resistance. Numerous models and factors have been proposed to elucidate the mechanism of palmitic acid (PA)-induced insulin resistance. However, proteomic studies of insulin resistance by HFD stimulation are usually performed under insulin conditions, leading to an unclear understanding of how a HFD alone affects hepatocytes. Here, we mapped the phosphorylation rewiring events in PA-stimulated HepG2 cells and found PA decreased the phosphorylation level of the eukaryotic translation initiation factor 4E-binding protein 2 (4EBP2) at S65/T70. Further experiments identified 4EBP2 as a key node of insulin resistance in either HFD mice or PA-treated cells. Reduced 4EBP2 levels increased glucose uptake and insulin sensitivity, whereas the 4EBP2_S65A/T70A mutation exacerbated PA-induced insulin resistance. Additionally, the nascent proteome revealed many glycolysis-related proteins translationally regulated by 4EBP2 such as hexokinase-2, pyruvate kinase PKM, TBC1 domain family member 4, and glucose-6-phosphate 1-dehydrogenase. In summary, we report the critical role of 4EBP2 in regulating HFD-stimulated insulin resistance in hepatocytes.

The influence of altruistic personality, interpersonal distance and social observation on prosocial behavior: An event-related potential (ERP) study.

The psychological mechanisms that high and low altruists exhibit in different contexts remain unknown. This study examined the underlying mechanisms of the effect of altruistic personality, social observation, and interpersonal distance on prosocial behavior using event-related potentials (ERPs). Participants with high and low altruism were asked to make prosocial or non-prosocial choices toward different interpersonal distances (friends, acquaintances, or strangers) under the (non)observer condition. The electrophysiological responses to the choice stimuli were simultaneously recorded. The behavioral results demonstrated that high altruists had more prosocial choices, and these choices were unaffected by interpersonal distance and social observation. However, low altruists made more prosocial choices toward friends and acquaintances under the observer than nonobserver conditions, whereas their prosocial choices toward strangers showed no difference. The ERP results demonstrated that low altruists showed more negative N2 when the choice stimuli were toward strangers and acquaintances or under the nonobserver condition. Furthermore, low altruists showed larger P3 under the observer than nonobserver conditions when the choice stimuli were toward friends and acquaintances, while this difference was absent when the choice stimuli were toward strangers. However, for high altruists, no effect of interpersonal distance and social observation was observed in N2 and P3. These results suggest that the prosocial behavior of low altruists is mainly driven by reputational incentives, whereas high altruists are primarily motivated by concern about the well-being of others. Our findings provide insights into the prosocial behavior of high and low altruists in different contexts and support the empathy-altruism hypothesis.

FOXE1 Contributes to the Development of Psoriasis by Regulating WNT5A.

Psoriasis is a common, chronic, and relapsing inflammatory skin disease characterized by hyperproliferation of keratinocytes (KCs) and infiltration of immune cells. The pathogenesis of psoriasis is complex, and the exact mechanism remains partially understood. In this study, we showed that the forkhead box family protein, FOXE1, had increased expression in lesional skins compared with nonlesional skin from patients with psoriasis. FOXE1 expression was also increased in an imiquimod-induced psoriatic mouse model as well as in M5-stimulated KCs. Using combinational approaches of knockdown and overexpression of FOXE1, we demonstrated that FOXE1 may promote the proliferation of KCs by facilitating G1/S transition and activating extracellular signal-regulated kinase 1/2 signaling pathway. In addition, knockdown of FOXE1 reduced the production of IL-1ß, IL-6, and TNF-α by KCs. RNA-sequencing profiling identified WNT5A as a potential downstream effector of FOXE1. Knockdown of WNT5A inhibited the proliferation of KCs; reduced the production of IL-1ß, IL-6, and TNF-α by KCs; and mitigated the growth-promoting effect of FOXE1 in FOXE1-overexpressed KCs. Finally, depletion of FOXE1 by lentiviral delivery of small hairpin RNAs or genetic approach ameliorated dermatitis symptoms in imiquimod-induced psoriasis-like mouse models. Taken together, our results indicated that FOXE1 participates in the pathogenesis of psoriasis and can serve as a target of psoriasis treatment.

Hydrogen Protection Boosts the Bioactivity of Chrysanthemum morifolium Extract in Preventing Palmitate-Induced Endothelial Dysfunction by Restoring MFN2 and Alleviating Oxidative Stress in HAEC Cells.

As the most important natural antioxidants in plant extracts, polyphenols demonstrate versatile bioactivities and are susceptible to oxidation. The commonly used ultrasonic extraction often causes oxidation reactions involving the formation of free radicals. To minimize the oxidation effects during the ultrasonic extraction process, we designed a hydrogen (H2)-protected ultrasonic extraction method and used it in Chrysanthemum morifolium extraction. Hydrogen-protected extraction improved the total antioxidant capacity, 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, and polyphenol content of Chrysanthemum morifolium water extract (CME) compared with air and nitrogen (N2) conditions. We further investigated the protective effects and mechanisms of CME on palmitate (PA)-induced endothelial dysfunction in human aorta endothelial cells (HAECs). We found that hydrogen-protected CME (H2-CME) best-prevented impairment in nitric oxide (NO) production, endothelial NO synthase (eNOS) protein level, oxidative stress, and mitochondrial dysfunction. In addition, H2-CME prevented PA-induced endothelial dysfunction by restoring mitofusin-2 (MFN2) levels and maintaining redox balance.

Social distance modulates the influence of social observation on pro-environmental behavior: An event-related potential (ERP) study.

Pro-environmental behavior benefits the environment but is individually costly. Therefore, understanding the neural processes of pro-environmental behavior can advance our knowledge of its implicit cost-benefit calculations and mechanisms. Previous studies have focused separately on the effects of social distance and social observation on explicit pro-environmental behavior responses, yet the underlying neurophysiological mechanism remains unknown. Using the event-related potentials (ERPs), we investigated the neural responses to the effects of social distance and social observation on pro-environmental behavior. Participants were instructed to decide between self-interest and pro-environmental choices towards different social distance targets (family members, acquaintances, or strangers) under observable and non-observable conditions. The behavioral results demonstrated that the rate of pro-environmental choices towards acquaintances and strangers was higher under the observable condition than under the non-observable condition. Nonetheless, the rate of pro-environmental choices was higher-unaffected by social observation-towards family members than towards acquaintances and strangers. The ERP results showed that the P2 and P3 amplitudes were smaller under the observable than under the non-observable condition when the potential bearers of environmental decisions were acquaintances and strangers. However, this difference did not emerge when the potential bearers of environmental decisions were family members. The ERP findings of smaller P2 and P3 amplitudes suggest that social observation may reduce the deliberate calculation of personal costs, thereby promoting individuals' pro-environmental behaviors towards acquaintances and strangers.

Environmental Protection or Self-Interest? The Public Accountability Moderates the Effects of Materialism and Advertising Appeals on the Pro-Environmental Behavior.

Background: Previous studies have examined the negative effects of materialism, which refers to the importance of possessing material wealth and image, on the pro-environmental behavior. Recently, a study found that highly materialistic individuals showed more pro-environmental behaviors involving self-benefit (vs other-benefit) appeals. However, previous studies ignored the role of public accountability. Purpose: This study aimed to explore the relationship between advertising appeals and the pro-environmental behavior of materialistic individuals in public (vs private) situations. Methods: This study used the material values scale to measure the materialistic extent and employed different advertising pictures. Meanwhile, Study 1(N=593) used the public cue, and Study 2 (N=622) used the eye cue to manipulate public accountability. Environmental donation was an indicator of the pro-environmental behavior. Results: Studies 1 and 2 found that the pro-environmental behavior of participants low in materialism was significantly higher than that of participants high in materialism involving other-benefit appeals, while this difference was not significant for pro-environmental behavior involving self-benefit appeals in the private situation. Participants with low and high materialism were not significantly different in the pro-environmental behavior involving self-benefit and other-benefit appeals in the public situation. Conclusion: The relationship between materialism and pro-environmental behavior involving self-benefit and other-benefit appeals can be moderated by the public accountability. In the private context, self-benefit appeals led materialistic people to engage in more pro-environmental behavior, while in the public context, the effectiveness of self-benefit and other-benefit appeals on the pro-environmental behavior of materialistic individuals was similar.

Risk decision: The self-charity discrepancies in electrophysiological responses to outcome evaluation.

Previous studies have examined the outcome evaluation related to the self and other, and recent research has explored the outcome evaluation of the self and other with pro-social implications. However, the evaluation processing of outcomes in the group in need remains unclear. This study has examined the neural mechanisms of evaluative processing by gambling for the self and charity, respectively. At the behavioral level, when participants make decisions for themselves, they made riskier decisions following the gain than loss in small outcomes and engage in more risky behaviors following the loss than gain in large outcomes. However, magnitude and valence did not affect the next risky behavior when participants made decisions for the charity. At the neurophysiological level, the results found that the FRN was larger for the charity outcome than for the self-outcome. For FRN, the valence difference of small outcomes was smaller than that of large outcomes. The P3 response was larger for the self-outcome than for the charity outcome. Meanwhile, compared with the small outcome, the self-charity discrepancies have a significant difference in large outcomes. In addition, the FRN amplitude for self in large outcomes was negatively correlated with the upcoming risky choices, regardless of outcome valence. The behavioral results suggest that people are more likely to optimize strategies for themselves than for the charity. The ERP findings indicated that people focus more on charity outcome than self-outcome in the early stage. In the middle and late stages, people turn attention to their outcomes, and the difference between self's and charity's outcome varies with the magnitude. Specifically, it is only in large outcomes that people engage more emotional attention or motivation in their outcomes, but self and charity outcomes had a similar emotional engagement in small outcomes.

Green Product Types Modulate Green Consumption in the Gain and Loss Framings: An Event-Related Potential Study.

People show a separation of intention and behavior in green consumption, and promoting actual green purchase behavior is more important than purchase intention. This study adopted a conflicting environmental decision paradigm to investigate behavioral and neural processes during actual green consumption decision-making involving different types of green products and message framing, according to construal level theory. Participants were instructed to make green consumption decisions involving green products with different psychological distances (self-interested green products vs. other-interested green products) under gain (e.g., buying green products brings positive results) or loss framing (e.g., not buying green products brings negative effects) while electroencephalograms were recorded. The behavioral results demonstrated that participants tended to purchase green products under loss framing more than under gain framing. The event-related potential results showed that under gain framing, decision-making for self-interested green products was associated with larger P3 than decision-making for other-interested green products. While under loss framing, decision-making for other-interested green products has a larger P260 than for self-interested green products. These findings suggest that under gain framing, self-interested green products elicit more cognitive resources than other-interested green products, while under loss framing, other-interested green products elicit stronger negative emotions than self-interested green products. The research has managerial implications for promoting consumers' actual purchase behavior.

Influence of Environmental Aesthetic Value and Anticipated Emotion on Pro-Environmental Behavior: An ERP Study.

Perceptual cues act as signals in the aesthetic value environment, which promote emotion regulation toward pro-environment behavior. This type of perception-emotion-behavior reactivity forms the core of human altruism. However, differences in pro-environmental behavior may result from variation across high-aesthetic-value (HAV) and low-aesthetic-value (LAV) environments. This study investigated the neural mechanisms underlying interaction effects between environmental context and emotion regulation on pro-environmental behavior by integrating behavioral and temporal dynamics of decision-making information processing with event-related potential (ERP) technique measures. The results indicated that changing anticipated emotions changes pro-environmental behavior. Regarding changing aesthetic value environments, while modulating emotion regulation, significant differences were found in brain regions and mean amplitudes of N1, P2, N2, and late positive potential (LPP) components, which anticipated emotion. The findings suggest that environmental aesthetic value and emotion regulation impact pro-environmental behavior.

Interpersonal distance modulates the influence of social observation on prosocial behaviour: An event-related potential (ERP) study.

This study aimed to explore the influence of interpersonal distance and social observation on prosocial behaviour. Participants were instructed to make costly prosocial decisions towards different interpersonal distance targets (friends, acquaintances or strangers) under the (non) observable condition, with simultaneous electroencephalogram recording. The behavioural results demonstrated that participants made more prosocial choices-unaffected by social observation-towards friends than towards acquaintances and strangers; nonetheless, participants made more prosocial choices towards acquaintances and strangers under the observable than under the non-observable condition. Event-related potential results showed that when participants made prosocial decisions towards friends, the P3 and N2 amplitudes remained unchanged between the observable and non-observable conditions; however, when participants made prosocial decisions towards acquaintances and strangers, a smaller N2 and a larger P3 were observed under the observable than those under the non-observable condition. These findings suggest that prosocial behaviour towards friends is driven by social preferences regarding the welfare of others, regardless of the possibility of reputation management. However, prosocial behaviour towards acquaintances and strangers might be motivated by a positive reputation, because individuals may bear in mind the potential future benefits.

The Effect of Preceding Self-Control on Green Consumption Behavior: The Moderating Role of Moral Elevation.

BACKGROUND: Studies have shown that individuals restrain their egoistic desires to benefit others (eg, the natural world), which require a higher-order psychological process, such as self-control. Therefore, performing a preceding self-control task may subsequently decrease green consumption behavior. However, whether and how moral elevation, which is an important type of positive incidental emotion, moderates the negative effect of exerting self-control on green consumption behavior remains unknown. PURPOSE: The present study aimed to examine how exerting self-control and moral elevation influenced green consumption behavior. METHODS: The product choice task that requires participants to make choices between buying environmentally friendly (eco-friendly) and cheaper (self-interest) products is an index of green consumption behavior. In Experiment 1, we adopted the incongruent Stroop task to induce the exertion of self-control, and participants were asked to make choices in the product choice task. In Experiment 2, participants were provided with moral elevating videos to elicit moral elevation during the interval between the Stroop and product choice tasks. RESULTS: Experiment 1 indicated that, relative to the congruent Stroop task (the control condition), completing the incongruent Stroop task led to less environmentally friendly choices. Experiment 2 indicated that the participants who watched the elevating video in the incongruent Stroop task condition chose environmentally friendly products with greater frequency compared to those who watched the neutral video. Furthermore, the analyses showed that self-reported moral elevation partly moderated the effect of the exertion of self-control on green consumption behavior. CONCLUSION: Our findings indicate that the exertion of self-control has a negative effect on green consumption behavior; however, moral elevation can counteract this negative effect of exerting self-control on green consumption behavior.

Cytotoxicity of Saikosaponin A targets HEKa cell through apoptosis induction by ROS accumulation and inflammation suppression via NF-κB pathway.

Saikosaponin A (SSA) is a triterpenoid saponin extracted from oriental medicinal plant Radix bupleuri, possessing various biological functions such as anti-inflammatory, immune regulation and anti-virus. This study aimed to explore therapeutic effects of SSA on psoriasis in both vitro and vivo. Our results showed that SSA increased reactive oxygen species (ROS) generation, and decreased mitochondrial membrane potential (MMP) and M5-induced inflammatory cytokines levels in HEKa cells in a dose-dependent manner. In addition, SSA promoted apoptosis and suppressed phosphorylation of NF-κB in vitro, which were restored by the ROS scavenger N-acetylcysteine (NAC). In imiquimod (IMQ)-induced mice, gavage with SSA markedly decreased Psoriasis Area and Severity Index (PASI) score and ameliorated epidermal hyperplasia through inhibition of NF-κB and NLRP3 signaling pathway. In conclusion, our studies demonstrate that SSA induces apoptosis and suppresses inflammation in HEKa cells and ameliorates IMQ-induced psoriasis in mice, making it a therapeutic candidate for psoriasis.

High ratio of ω-3/ω-6 polyunsaturated fatty acids targets mTORC1 to prevent high-fat diet-induced metabolic syndrome and mitochondrial dysfunction in mice.

Adjusting ω-3/ω-6 polyunsaturated fatty acids (PUFAs) ratio in high-fat diet is one potential mean to improve metabolic syndrome; however, underlying mechanisms remain unclear. Four groups of mice were fed 60% kcal diets with saturated fatty acids, three different ω-3/ω-6 PUFAs ratios (low, middle and high) for 12 weeks, respectively. Body weight, atherosclerosis marker, insulin signal index and level of lipid accumulation in liver were significantly lowered in High group compared with saturated fatty acids group and Low group at week 12. Expressions of p-mTOR and raptor were inhibited by high ω-3 PUFAs. Importantly, ω-3 PUFAs intake up-regulated mitochondrial electron transport chain and tricarboxylic acid cycle pathway through metabolomics analysis in liver. Mitochondrial complexes activities were raised, fumaric acid was reduced and oxidative stress was alleviated in High group. We conclude that consuming long-term high-fat diet with same calories but high ω-3/ω-6 PUFAs ratio relieves metabolic syndrome by regulating mTORC1 pathway to enhance mitochondrial function.

L-Arabinose Elicits Gut-Derived Hydrogen Production and Ameliorates Metabolic Syndrome in C57BL/6J Mice on High-Fat-Diet.

Obesity and metabolic syndrome (MS) associated with excess calorie intake has become a great public health concern worldwide. L-arabinose, a naturally occurring plant pentose, has a promising future as a novel food ingredient with benefits in MS; yet the mechanisms remain to be further elucidated. Gut microbiota is recently recognized to play key roles in MS. Molecular hydrogen, an emerging medical gas with reported benefits in MS, can be produced and utilized by gut microbes. Here we show oral L-arabinose elicited immediate and robust release of hydrogen in mice in a dose-and-time-dependent manner while alleviating high-fat-diet (HFD) induced MS including increased body weight especially fat weight, impaired insulin sensitivity, liver steatosis, dyslipidemia and elevated inflammatory cytokines. Moreover, L-arabinose modulated gene-expressions involved in lipid metabolism and mitochondrial function in key metabolic tissues. Antibiotics treatment abolished L-arabinose-elicited hydrogen production independent of diet type, confirming gut microbes as the source of hydrogen. q-PCR of fecal 16S rDNA revealed modulation of relative abundances of hydrogen-producing and hydrogen-consuming gut microbes as well as probiotics by HFD and L-arabinose. Our data uncovered modulating gut microbiota and hydrogen yield, expression of genes governing lipid metabolism and mitochondrial function in metabolic tissues is underlying L-arabinose's benefits in MS.