Nitric oxide : biology and chemistry最新文献

{"title":"Cystathionine gamma-lyase deficiency exaggerates diethylnitrosamine-induced liver damage in mice","authors":"Samantha Ligi ,&nbsp;Arm Ali ,&nbsp;Guangdong Yang","doi":"10.1016/j.niox.2024.08.001","DOIUrl":"10.1016/j.niox.2024.08.001","url":null,"abstract":"<div><p>Cystathionine gamma-lyase (CSE) is a key enzyme in reverse transsulfuration pathway and contributes to the majority of H₂S generation in liver tissues via cysteine metabolism. Dysfunction of the CSE/H₂S system is linked to both chronic and acute liver damage. This study investigated the regulatory role of CSE deficiency on diethylnitrosamine (DEN)-induced liver damage in mice. A single injection of DEN was administered into 4-week-old male CSE knockout (CSE-KO) mice and wild-type (WT) littermates, and the mice were sacrificed at 28 weeks of age. Compared to age-matched WT mice, CSE-KO mice spontaneously developed steatosis with increased oxidative stress and higher expressions of inflammation and fibrosis-related genes at 28-weeks of age. Following DEN injection, CSE-KO mice experienced more severe liver damage in comparison with the WT group as reflected by elevated levels of lipid accumulation, increased activities of alanine aminotransferase and aspartate aminotransferase, higher oxidative stress and fibrosis development, and increased expressions of inflammation and fibrosis-related genes. No visible tumors were observed in both types of mice with DEN treatment. In addition, the expression levels of the three H₂S-generating proteins (CSE, cystathionine beta-synthase, and 3-mercaptopyruvate sulfurtransferase) and the H₂S production rate in liver tissues were unaffected by DEN. Taken together, our study demonstrates that CSE provides a significant hepatoprotective effect and deficiency of CSE exaggerates DEN-induced liver damage in mice. Based on these findings, it can be suggested that targeting the CSE/H₂S signaling pathway could be a potential therapeutic target for the treatment of liver diseases.</p></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":"151 ","pages":"Pages 1-9"},"PeriodicalIF":3.2,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141996226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The hemodynamic response to nitrite is acute and dependent upon tissue perfusion","authors":"Luke S. Dunaway ,&nbsp;Khatera Saii ,&nbsp;Anthea LoBue ,&nbsp;Shruthi Nyshadham ,&nbsp;Nasim Abib ,&nbsp;Sophia K. Heuser ,&nbsp;Skylar A. Loeb ,&nbsp;Ulf Simonsen ,&nbsp;Miriam M. Cortese-Krott ,&nbsp;Brant E. Isakson","doi":"10.1016/j.niox.2024.07.005","DOIUrl":"10.1016/j.niox.2024.07.005","url":null,"abstract":"<div><p>In the vasculature, nitric oxide (NO) is produced in the endothelium by endothelial nitric oxide synthase (eNOS) and is critical for the regulation of blood flow and blood pressure. Blood flow may also be regulated by the formation of nitrite-derived NO catalyzed by hemoproteins under hypoxic conditions. We sought to investigate whether nitrite administration may affect tissue perfusion and systemic hemodynamics in WT and eNOS knockout mice. We found that global eNOS KO mice show decreased tissue perfusion compared to WT mice by using laser speckle contrast imaging. To study both the acute and long-term effects of sodium nitrite (0, 0.1, 1, and 10 mg/kg) on peripheral blood flow and systemic blood pressure, a bolus of nitrite was delivered intraperitoneally every 24 h over 4 consecutive days. We found that nitrite administration resulted in a dose-dependent and acute increase in peripheral blood flow in eNOS KO mice but had no effects in WT mice. The nitrite induced changes in tissue perfusion were transient, as determined by intraindividual comparisons of tissue perfusion 24-h after injection. Accordingly, 10 mg/kg sodium nitrite acutely decreased blood pressure in eNOS KO mice but not in WT mice as determined by invasive Millar catheterization. Interestingly, we found the vasodilatory effects of nitrite to be inversely correlated to baseline tissue perfusion. These results demonstrate the nitrite acutely recovers hypoperfusion and hypertension in global eNOS KO mice and suggest the vasodilatory actions of nitrite are dependent upon tissue hypoperfusion.</p></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":"150 ","pages":"Pages 47-52"},"PeriodicalIF":3.2,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141889801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spraying with encapsulated nitric oxide donor reduces weight loss and oxidative damage in papaya fruit","authors":"Julia C. da Veiga ,&nbsp;Neidiquele M. Silveira ,&nbsp;Amedea B. Seabra ,&nbsp;Joana C. Pieretti ,&nbsp;Yolanda Boza ,&nbsp;Angelo P. Jacomino ,&nbsp;Júlio César Z. Filho ,&nbsp;Vinícius P. Campagnoli ,&nbsp;Patrícia Cia ,&nbsp;Ilana U. Bron","doi":"10.1016/j.niox.2024.07.004","DOIUrl":"10.1016/j.niox.2024.07.004","url":null,"abstract":"<div><p>The combination of nitric oxide (NO) donors with nanomaterials has emerged as a promising approach to reduce postharvest losses. The encapsulation of NO donors provides protection from rapid degradation and controlled release, enhancing the NO effectiveness in postharvest treatments. Moreover, the application method can also influence postharvest responses. In this study, two application methods were evaluated, spraying and immersion, using <em>S</em>-nitrosoglutathione (GSNO, a NO donor) in free and encapsulated forms on papaya fruit. Our hypothesis was that GSNO encapsulated in chitosan nanoparticles would outperform the free form in delaying fruit senescence. In addition, this study marks the pioneering characterization of chitosan nanoparticles containing GSNO within the framework of a postharvest investigation. Overall, our findings indicate that applying encapsulated GSNO (GSNO-NP-S) through spraying preserves the quality of papaya fruit during storage. This method not only minimizes weight loss, ethylene production, and softening, but also stimulates antioxidant responses, thereby mitigating oxidative damage. Consequently, it stands out as the promising technique for delaying papaya fruit senescence. This innovative approach holds the potential to enhance postharvest practices and advance sustainable agriculture.</p></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":"150 ","pages":"Pages 37-46"},"PeriodicalIF":3.2,"publicationDate":"2024-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141748676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of nitrate supplementation on oxygen saturation levels for acute mountain sickness prevention: A systematic review and meta-analysis","authors":"Muhammad Rizqi Tri Nafi'an ,&nbsp;Rahmaningsih Mara Sabirin ,&nbsp;Rakhmat Ari Wibowo ,&nbsp;Meida Sofyana ,&nbsp;Imtiyaz Hafizah Zahra ,&nbsp;Danindra Ario Wiryawan ,&nbsp;Qonita Jayanti Wijayatno ,&nbsp;Abdul Rohman","doi":"10.1016/j.niox.2024.07.003","DOIUrl":"10.1016/j.niox.2024.07.003","url":null,"abstract":"<div><h3>Purpose</h3><p>This study aimed to systematically review the effect of nitrate supplementation on blood oxygen saturation<strong>.</strong></p></div><div><h3>Methods</h3><p>We searched PubMed, Scopus, and Cochrane Library databases from their inception up to October 2022. Two reviewers independently conducted two stages of the screening process to include a randomized controlled trial with nitrate supplementation versus placebo intervention assessing oxygen saturation among lowlanders going to either real or simulated high altitude environments. We used the Cochrane Risk of Bias 2.0 tool to assess the risk of bias in the included studies. Fixed-effect model meta-analyses were conducted for laboratory-based studies. Random-effect meta-analyses were conducted for real-world studies.</p></div><div><h3>Results</h3><p>We found 7 trials that met the eligibility criteria. A meta-analysis of studies with some bias concerns showed an increase of 1.26 % in the SpO2 with 44 % I² during submaximal exercise at simulated high altitudes (GRADE: low). On the contrary, a meta-analysis of studies without heterogeneity showed that nitrate supplementation aggravated oxygen saturation decline (−2.64 %, p = 0.03, GRADE: high) during rest in real high-altitude environments. A meta-analysis also showed that nitrate supplementation did not affect Acute Mountain Sickness (AMS) symptoms (GRADE: high).</p></div><div><h3>Conclusion</h3><p>Our results suggest that nitrate supplementation did not provide benefits for AMS prevention during rest at high altitudes. The low-quality evidence showing small beneficial effects of nitrate supplementation during exercise calls for further studies.</p></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":"150 ","pages":"Pages 27-36"},"PeriodicalIF":3.2,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141603992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unlocking the versatility of nitric oxide in plants and insights into its molecular interplays under biotic and abiotic stress","authors":"Ritu Kumari ,&nbsp;Preedhi Kapoor ,&nbsp;Bilal Ahmad Mir ,&nbsp;Maninder Singh ,&nbsp;Zubair Ahmad Parrey ,&nbsp;Gurseen Rakhra ,&nbsp;Parul Parihar ,&nbsp;M. Nasir Khan ,&nbsp;Gurmeen Rakhra","doi":"10.1016/j.niox.2024.07.002","DOIUrl":"10.1016/j.niox.2024.07.002","url":null,"abstract":"<div><p>In plants, nitric oxide (NO) has become a versatile signaling molecule essential for mediating a wide range of physiological processes under various biotic and abiotic stress conditions. The fundamental function of NO under various stress scenarios has led to a paradigm shift in which NO is now seen as both a free radical liberated from the toxic product of oxidative metabolism and an agent that aids in plant sustenance. Numerous studies on NO biology have shown that NO is an important signal for germination, leaf senescence, photosynthesis, plant growth, pollen growth, and other processes. It is implicated in defense responses against pathogensas well as adaptation of plants in response to environmental cues like salinity, drought, and temperature extremes which demonstrates its multifaceted role. NO can carry out its biological action in a variety of ways, including interaction with protein kinases, modifying gene expression, and releasing secondary messengers. In addition to these signaling events, NO may also be in charge of the chromatin modifications, nitration, and S-nitrosylation-induced posttranslational modifications (PTM) of target proteins. Deciphering the molecular mechanism behind its essential function is essential to unravel the regulatory networks controlling the responses of plants to various environmental stimuli. Taking into consideration the versatile role of NO, an effort has been made to interpret its mode of action based on the post-translational modifications and to cover shreds of evidence for increased growth parameters along with an altered gene expression.</p></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":"150 ","pages":"Pages 1-17"},"PeriodicalIF":3.2,"publicationDate":"2024-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141555232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of hydrogen sulfide in dermatological diseases","authors":"","doi":"10.1016/j.niox.2024.07.001","DOIUrl":"10.1016/j.niox.2024.07.001","url":null,"abstract":"<div><p>Hydrogen sulfide (H₂S), together with carbon monoxide (CO) and nitric oxide (NO), is recognized as a vital gasotransmitter. H₂S is biosynthesized by enzymatic pathways in the skin and exerts significant physiological effects on a variety of biological processes, such as apoptosis, modulation of inflammation, cellular proliferation, and regulation of vasodilation. As a major health problem, dermatological diseases affect a large proportion of the population every day. It is urgent to design and develop effective drugs to deal with dermatological diseases. Dermatological diseases can arise from a multitude of etiologies, including neoplastic growth, infectious agents, and inflammatory processes. The abnormal metabolism of H₂S is associated with many dermatological diseases, such as melanoma, fibrotic diseases, and psoriasis, suggesting its therapeutic potential in the treatment of these diseases. In addition, therapies based on H₂S donors are being developed to treat some of these conditions. In the review, we discuss recent advances in the function of H₂S in normal skin, the role of altering H₂S metabolism in dermatological diseases, and the therapeutic potential of diverse H₂S donors for the treatment of dermatological diseases.</p></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":"150 ","pages":"Pages 18-26"},"PeriodicalIF":3.2,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141545117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Carbon monoxide-releasing Vehicle CO@TPyP-FeMOFs modulating macrophages phenotype in inflammatory wound healing","authors":"Yixian Mu ,&nbsp;Xinlei Yang ,&nbsp;Yinhong Xie ,&nbsp;Jie Luo ,&nbsp;Sui Wu ,&nbsp;JinMing Yang ,&nbsp;Wei Zhao ,&nbsp;Junying Chen ,&nbsp;Yajun Weng","doi":"10.1016/j.niox.2024.06.005","DOIUrl":"10.1016/j.niox.2024.06.005","url":null,"abstract":"<div><p>Healing of chronic wounds has been critically limited by prolonged inflammation. Carbon monoxide (CO) is a biologically active molecule with high potential based on its efficacy in modulating inflammation, promoting wound healing and tissue remodeling. Strategies to use CO as a gaseous drug to chronic wounds have emerged, but controlling the sustained release of CO at the wound site remains a major challenge. In this work, a porphyrin-Fe based metal organic frameworks, TPyP-FeMOFs was prepared. The synthesized TPyP-FeMOFs was high-temperature vacuum activated (AcTPyP-FeMOFs) and AcTPyP-FeMOFs had a relatively high Fe (II) content. CO sorption isotherms showed that AcTPyP-FeMOFs chemisorbed CO and thus CO release was sustained and prolonged. In vitro evaluation results showed that CO@TPyP-FeMOFs reduced the inflammatory level of lipopolysaccharide (LPS) activated macrophages, polarized macrophages to M2 anti-inflammatory phenotype, and promoted the proliferation of fibroblasts by altering the pathological microenvironment. In vivo study confirmed CO@TPyP-FeMOFs promoted healing in a LPS model of delayed cutaneous wound repair and reduced macrophages and neutrophils recruitment. Both in vitro and in vivo studies verified that CO@TPyP-FeMOFs acted on macrophages by modulating phenotype and inflammatory factor expression. Thus, CO release targeting macrophages and pathological microenvironment modulation presented a promising strategy for wound healing.</p></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":"149 ","pages":"Pages 49-59"},"PeriodicalIF":3.9,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141420095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sodium thiosulfate: A donor or carrier signaling molecule for hydrogen sulfide?","authors":"Si-Miao Tang ,&nbsp;Guo-Zhong Lu ,&nbsp;Xiao-Yong Lei ,&nbsp;Xiao-Yan Yang ,&nbsp;Guo-Tao Tang ,&nbsp;Jia Yu ,&nbsp;Zhi-Zhong Xie","doi":"10.1016/j.niox.2024.06.004","DOIUrl":"10.1016/j.niox.2024.06.004","url":null,"abstract":"<div><p>Sodium thiosulfate has been used for decades in the treatment of calciphylaxis and cyanide detoxification, and has recently shown initial therapeutic promise in critical diseases such as neuronal ischemia, diabetes mellitus, heart failure and acute lung injury. However, the precise mechanism of sodium thiosulfate remains incompletely defined and sometimes contradictory. Although sodium thiosulfate has been widely accepted as a donor of hydrogen sulfide (H₂S), emerging findings suggest that it is the executive signaling molecule for H₂S and that its effects may not be dependent on H₂S. This article presents an overview of the current understanding of sodium thiosulfate, including its synthesis, biological characteristics, and clinical applications of sodium thiosulfate, as well as the underlying mechanisms <em>in vivo</em>. We also discussed the interplay of sodium thiosulfate and H₂S. Our review highlights sodium thiosulfate as a key player in sulfide signaling with the broad clinical potential for the future.</p></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":"149 ","pages":"Pages 67-74"},"PeriodicalIF":3.2,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141427357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of continuous low-dose and high-dose burst of inhaled nitric oxide in spontaneously breathing COVID-19 patients: A randomized controlled trial","authors":"Nikolay O. Kamenshchikov ,&nbsp;Bijan Safaee Fakhr ,&nbsp;Igor V. Kravchenko ,&nbsp;Andrey Yu Dish ,&nbsp;Yuri K. Podoksenov ,&nbsp;Boris N. Kozlov ,&nbsp;Tatiana P. Kalashnikova ,&nbsp;Mark A. Tyo ,&nbsp;Nina D. Anfinogenova ,&nbsp;Alla A. Boshchenko ,&nbsp;Lorenzo Berra","doi":"10.1016/j.niox.2024.06.003","DOIUrl":"10.1016/j.niox.2024.06.003","url":null,"abstract":"<div><h3>Background</h3><p>Inhaled nitric oxide (iNO) showed to improve oxygenation at low doses by reducing intrapulmonary shunt and to display antiviral properties at high doses. To assess the safety and potential benefits, we designed an exploratory clinical trial comparing low-dose with intermittent high-dose iNO to only intermittent high-dose iNO in hypoxemic COVID-19 patients.</p></div><div><h3>Methods</h3><p>In this single-center interventional non-inferiority randomized trial (<span>ClinicalTrials.gov</span><svg><path></path></svg>, NCT04476992), twenty oxygen-dependent COVID-19 patients were randomly assigned to the high-dose (200 ppm for 30 min) + continuous low-dose (20 ppm) iNO group (iNO_200/20) or the high-dose iNO group (iNO₂₀₀). Methemoglobinemia (MetHb) assessed 48 h after iNO initiation was the primary endpoint. Reverse-transcription polymerase chain reaction for SARS-CoV-2, inflammatory markers during hospitalization, and heart ultrasounds during the iNO₂₀₀ treatments were evaluated.</p></div><div><h3>Results</h3><p>MetHb difference between iNO groups remained within the non-inferiority limit of 3 %, indicating comparable treatments despite being statistically different (p-value&lt;0.01). Both groups presented similar SpO₂/FiO₂ ratio at 48 h (iNO₂₀₀ vs. iNO_200/20 341[334–356] vs. 359 [331–380], respectively, p-value = 0.436). Both groups showed the same time to SARS-CoV-2 negativization, hospital length of stay, and recovery time. iNO-treated patients showed quicker SARS-CoV-2 negativization compared to a similar group of non-iNO patients (HR 2.57, 95%CI 1.04–6.33). During the 228 treatments, iNO₂₀₀ and iNO_200/20 groups were comparable for safety, hemodynamic stability, and respiratory function improvement.</p></div><div><h3>Conclusions</h3><p>iNO_200/20 and iNO₂₀₀ are equally safe in non-intubated patients with COVID-19-induced respiratory failure with regards to MetHb and NO₂. Larger studies should investigate whether iNO_200/20 leads to better outcomes compared to non-iNO treated patients.</p></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":"149 ","pages":"Pages 41-48"},"PeriodicalIF":3.9,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141331519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adipocyte-specific Nrf2 deletion negates nitro-oleic acid benefits on glucose tolerance in diet-induced obesity","authors":"D.V. Chartoumpekis ,&nbsp;I. Chen ,&nbsp;S.R. Salvatore ,&nbsp;F.J. Schopfer ,&nbsp;B.A. Freeman ,&nbsp;N.K.H. Khoo","doi":"10.1016/j.niox.2024.06.002","DOIUrl":"10.1016/j.niox.2024.06.002","url":null,"abstract":"<div><p>Obesity is commonly linked with white adipose tissue (WAT) dysfunction, setting off inflammation and oxidative stress, both key contributors to the cardiometabolic complications associated with obesity. To improve metabolic and cardiovascular health, countering these inflammatory and oxidative signaling processes is crucial. Offering potential in this context, the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) by nitro-fatty acids (NO₂-FA) promote diverse anti-inflammatory signaling and counteract oxidative stress. Additionally, we previously highlighted that nitro-oleic acid (NO₂-OA) preferentially accumulates in WAT and provides protection against already established high fat diet (HFD)-mediated impaired glucose tolerance. The precise mechanism accounting for these protective effects remained largely unexplored until now. Herein, we reveal that protective effects of improved glucose tolerance by NO₂-OA is absent when Nrf2 is specifically ablated in adipocytes (ANKO mice). NO₂-OA treatment did not alter body weight between ANKO and littermate controls (Nrf2^fl/fl) mice on both the HFD and low-fat diet (LFD). As expected, at day 76 (before NO₂-OA treatment) and notably at day 125 (daily treatment of 15 mg/kg NO₂-OA for 48 days), both HFD-fed Nrf2^fl/fl and ANKO mice exhibited increased fat mass and reduced lean mass compared to LFD controls. However, throughout the NO₂-OA treatment, no distinction was observed between Nrf2^fl/fl and ANKO in the HFD-fed mice as well as in the Nrf2^fl/fl mice fed a LFD. Glucose tolerance tests revealed impaired glucose tolerance in HFD-fed Nrf2^fl/fl and ANKO compared to LFD-fed Nrf2^fl/fl mice. Notably, NO₂-OA treatment improved glucose tolerance in HFD-fed Nrf2^fl/fl but did not yield the same improvement in ANKO mice at days 15, 30, and 55 of treatment. Unraveling the pathways linked to NO₂-OA's protective effects in obesity-mediated impairment in glucose tolerance is pivotal within the realm of precision medicine, crucially propelling future applications and refining novel drug-based strategies.</p></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":"149 ","pages":"Pages 75-84"},"PeriodicalIF":3.2,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1089860324000776/pdfft?md5=ad2f79fdb7ebaa2e2587ac6ddb7537ad&pid=1-s2.0-S1089860324000776-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141327717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}