{"title":"Epigenetic reprogramming of mtDNA and its etiology in mitochondrial diseases.","authors":"Anil Kumar, Anita Choudhary, Anjana Munshi","doi":"10.1007/s13105-024-01032-z","DOIUrl":"10.1007/s13105-024-01032-z","url":null,"abstract":"<p><p>Mitochondrial functionality and its regulation are tightly controlled through a balanced crosstalk between the nuclear and mitochondrial DNA interactions. Epigenetic signatures like methylation, hydroxymethylation and miRNAs have been reported in mitochondria. In addition, epigenetic signatures encoded by nuclear DNA are also imported to mitochondria and regulate the gene expression dynamics of the mitochondrial genome. Alteration in the interplay of these epigenetic modifications results in the pathogenesis of various disorders like neurodegenerative, cardiovascular, metabolic disorders, cancer, aging and senescence. These modifications result in higher ROS production, increased mitochondrial copy number and disruption in the replication process. In addition, various miRNAs are associated with regulating and expressing important mitochondrial gene families like COX, OXPHOS, ND and DNMT. Epigenetic changes are reversible and therefore therapeutic interventions like changing the target modifications can be utilized to repair or prevent mitochondrial insufficiency by reversing the changed gene expression. Identifying these mitochondrial-specific epigenetic signatures has the potential for early diagnosis and treatment responses for many diseases caused by mitochondrial dysfunction. In the present review, different mitoepigenetic modifications have been discussed in association with the development of various diseases by focusing on alteration in gene expression and dysregulation of specific signaling pathways. However, this area is still in its infancy and future research is warranted to draw better conclusions.</p>","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":" ","pages":"727-741"},"PeriodicalIF":3.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141306176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gabriela Neira, Javier Gómez-Ambrosi, Javier A Cienfuegos, Beatriz Ramírez, Sara Becerril, Amaia Rodríguez, María A Burrell, Jorge Baixauli, Amaia Mentxaka, Marcos Casado, Camilo Silva, Javier Escalada, Gema Frühbeck, Victoria Catalán
{"title":"Increased expression of IL-1β in adipose tissue in obesity influences the development of colon cancer by promoting inflammation.","authors":"Gabriela Neira, Javier Gómez-Ambrosi, Javier A Cienfuegos, Beatriz Ramírez, Sara Becerril, Amaia Rodríguez, María A Burrell, Jorge Baixauli, Amaia Mentxaka, Marcos Casado, Camilo Silva, Javier Escalada, Gema Frühbeck, Victoria Catalán","doi":"10.1007/s13105-024-01048-5","DOIUrl":"https://doi.org/10.1007/s13105-024-01048-5","url":null,"abstract":"<p><p>Excess adiposity contributes to the development of colon carcinoma (CC). Interleukin (IL)-1β is a pro-inflammatory cytokine relevant in obesity-associated chronic inflammation and tumorigenic processes. We herein aimed to study how obesity and CC affects the expression of IL1B, and to determine the impact of IL-1β on the regulation of metabolic inflammation and gut barrier function in the context of obesity and CC. Samples from 71 volunteers were used in a case-control study and a rat model of diet-induced obesity (DIO). Furthermore, bariatric surgery was used to determine the effect of weight loss on the intestinal gene expression levels of Il1b. To evaluate the effect of IL-1β and obesity in CC, we treated the adenocarcinoma cell line HT-29 with IL-1β and the adipocyte-conditioned medium (ACM) from patients with obesity. We showed that obesity (P < 0.05) and CC (P < 0.01) upregulated the transcript levels of IL1B in visceral adipose tissue as well as in the colon from patients with CC (P < 0.01). The increased expression of Il1b in the ileum and colon in DIO rats decreased after weight loss achieved by either sleeve gastrectomy or caloric restriction (both P < 0.05). ACM treatment on HT-29 cells upregulated (P < 0.05) the transcripts of IL1B and CCL2, while reducing (P < 0.05) the expression of the anti-inflammatory ADIPOQ and MUC2 genes. Additionally, IL-1β upregulated (P < 0.01) the expression of CCL2 and TNF whilst downregulating (P < 0.01) the transcript levels of IL4, ADIPOQ and TJP1 in HT-29 cells. We provide evidence of the important role of IL-1β in obesity-associated CC by directly promoting inflammation.</p>","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Savera Aggarwal, Archana Rastogi, Rakhi Maiwall, Jayesh K Sevak, Vipin Yadav, Jaswinder Maras, Sherin Sarah Thomas, Pratibha R Kale, Viniyendra Pamecha, Nagarajan Perumal, Nirupama Trehanpati, Gayatri Ramakrishna
{"title":"Palmitic acid causes hepatocyte inflammation by suppressing the BMAL1-NAD+-SIRT2 axis","authors":"Savera Aggarwal, Archana Rastogi, Rakhi Maiwall, Jayesh K Sevak, Vipin Yadav, Jaswinder Maras, Sherin Sarah Thomas, Pratibha R Kale, Viniyendra Pamecha, Nagarajan Perumal, Nirupama Trehanpati, Gayatri Ramakrishna","doi":"10.1007/s13105-024-01042-x","DOIUrl":"https://doi.org/10.1007/s13105-024-01042-x","url":null,"abstract":"<p>Palmitic acid is the most abundant saturated fatty acid in circulation and causes hepatocyte toxicity and inflammation. As saturated fatty acid can also disrupt the circadian rhythm, the present work evaluated the connection between clock genes and NAD+ dependent Sirtuins in protecting hepatocytes from lipid-induced damage. Hepatocytes (immortal cells PH5CH8, hepatoma cells HepG2) treated with higher doses of palmitic acid (400-600μM) showed typical features of steatosis accompanied with growth inhibition and increased level of inflammatory markers (IL-6 IL-8, IL-1α and IL-1β) together with decline in NAD+ levels. Palmitic acid treated hepatocytes showed significant decline in not only the protein levels of SIRT2 but also its activity as revealed by the acetylation status of its downstream targets (Tubulin and NF-ƙB). Additionally, the circadian expression of both SIRT2 and BMAL1 was inhibited in presence of palmitic acid in only the non-cancerous hepatocytes, PH5CH8 cells. Clinical specimens obtained from subjects with NASH-associated fibrosis, ranging from absent (F0) to cirrhosis (F4), showed a significant decline in levels of SIRT2 and BMAL1, especially in the cirrhotic liver. Ectopic expression of BMAL1 or activating SIRT2 by supplementation with nicotinamide riboside (precursor of NAD+) dampened the palmitic acid induced lipoinflammation and lipotoxicity more effectively in PH5CH8 cells as compared to HepG2 cells. Mechanistically, palmitic acid caused transcriptional suppression of SIRT2 by disrupting the chromatin occupancy of BMAL1 at its promoter site. Overall, the work suggested that SIRT2 is a clock-controlled gene that is transcriptionally regulated by BMAL1. In conclusion the activation of the BMAL1-NAD+-SIRT2 axis shows hepatoprotective effects by preventing lipotoxicity and dampening inflammation.</p>","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":"193 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142257101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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 Irisin in exercise training-regulated endoplasmic reticulum stress, autophagy and myogenesis in the skeletal muscle after myocardial infarction","authors":"Shou Pan, Wujing Ren, Yifang Zhao, Mengxin Cai, Zhenjun Tian","doi":"10.1007/s13105-024-01049-4","DOIUrl":"https://doi.org/10.1007/s13105-024-01049-4","url":null,"abstract":"<p>Patients with heart failure (HF) are often accompanied by skeletal muscle abnormalities, which can lead to exercise intolerance and compromise daily activities. Irisin, an exercise training (ET) -induced myokine, regulates energy metabolism and skeletal muscle homeostasis. However, the precise role of Irisin in the benefits of ET on inhibiting skeletal muscle atrophy, particularly on endoplasmic reticulum (ER) stress, autophagy, and myogenesis following myocardial infarction (MI) remains unclear. In this study, we investigated the expression of Irisin protein in wild-type mice with MI, and assessed its role in the beneficial effects of ET using an <i>Fndc5</i> knockout mice. Our findings revealed that MI reduced muscle fiber cross-sectional area (CSA), while downregulating the expression of Irisin, PGC-1α and SOD1. Concurrently, MI elevated the levels of ER stress and apoptosis, and inhibited autophagy in skeletal muscle. Conversely, ET mitigated ER stress and apoptosis in the skeletal muscle of infarcted mice. Notably, <i>Fndc5</i> knockout worsened MI-induced ER stress and apoptosis, suppressed autophagy and myogenesis, and abrogated the beneficial effects of ET. In conclusion, our findings highlight the role of Irisin in the ET-mediated alleviation of skeletal muscle abnormalities. This study provides valuable insights into MI-induced muscle abnormalities and enhances our understanding of exercise rehabilitation mechanisms in clinical MI patients.</p>","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":"19 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142257103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jinchunzi Yang, Elisa Félix-Soriano, Alejandro Martínez-Gayo, Javier Ibañez-Santos, Neira Sáinz, J Alfredo Martínez, María J. Moreno-Aliaga
{"title":"SIRT1 and FOXO1 role on MASLD risk: effects of DHA-rich n-3 PUFA supplementation and exercise in aged obese female mice and in post-menopausal overweight/obese women","authors":"Jinchunzi Yang, Elisa Félix-Soriano, Alejandro Martínez-Gayo, Javier Ibañez-Santos, Neira Sáinz, J Alfredo Martínez, María J. Moreno-Aliaga","doi":"10.1007/s13105-024-01044-9","DOIUrl":"https://doi.org/10.1007/s13105-024-01044-9","url":null,"abstract":"<p>Sirtuins 1 (SIRT1) and Forkhead box protein O1 (FOXO1) expression have been associated with obesity and metabolic dysfunction-associated steatotic liver disease (MASLD). Exercise and/or docosahexaenoic acid (DHA) supplementation have shown beneficial effects on MASLD. The current study aims to assess the relationships between <i>Sirt1</i>, <i>Foxo1</i> mRNA levels and several MASLD biomarkers, as well as the effects of DHA-rich n-3 PUFA supplementation and/or exercise in the steatotic liver of aged obese female mice, and in peripheral blood mononuclear cells (PBMCs) of postmenopausal women with overweight/obesity. In the liver of 18-month-old mice, <i>Sirt1</i> levels positively correlated with the expression of genes related to fatty acid oxidation, and negatively correlated with lipogenic and proinflammatory genes. Exercise (long-term treadmill training), especially when combined with DHA, upregulated hepatic <i>Sirt1</i> mRNA levels. Liver <i>Foxo1</i> mRNA levels positively associated with hepatic triglycerides (TG) content and the expression of lipogenic and pro-inflammatory genes, while negatively correlated with the lipolytic gene <i>Hsl</i>. In PBMCs of postmenopausal women with overweight/obesity, <i>FOXO1</i> mRNA expression negatively correlated with the hepatic steatosis index (HSI) and the Zhejiang University index (ZJU). After 16-weeks of DHA-rich PUFA supplementation and/or progressive resistance training (RT), most groups exhibited reduced MASLD biomarkers and risk indexes accompanying with body fat mass reduction, but no significant changes were found between the intervention groups. However, in PBMCs n-3 supplementation upregulated <i>FOXO1</i> expression, and the RT groups exhibited higher <i>SIRT1</i> expression. In summary, SIRT1 and FOXO1 could be involved in the beneficial mechanisms of exercise and n-3 PUFA supplementation related to MASLD manifestation.</p>","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":"105 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142175625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Inmaculada Aguilera-Buenosvinos, Miguel A Martínez-González, Andrea Romanos-Nanclares, Rodrigo Sánchez-Bayona, Carlos E de Andrea, Ligia J Domínguez, Estefania Toledo
{"title":"Dietary-Based Diabetes Risk Score and breast cancer: a prospective evaluation in the SUN project.","authors":"Inmaculada Aguilera-Buenosvinos, Miguel A Martínez-González, Andrea Romanos-Nanclares, Rodrigo Sánchez-Bayona, Carlos E de Andrea, Ligia J Domínguez, Estefania Toledo","doi":"10.1007/s13105-024-01036-9","DOIUrl":"https://doi.org/10.1007/s13105-024-01036-9","url":null,"abstract":"<p><p>An association between type 2 diabetes (T2D) and breast cancer risk has been reported. This association can be potentially explained by alteration of the insulin/IGF system. Therefore, we aimed to prospectively investigate whether a previously reported Dietary-Based Diabetes Risk Score (DDS) inversely associated with T2D was also associated with breast cancer risk in the SUN (\"Seguimiento Universidad de Navarra\") cohort. We followed up 10,810 women (mean age = 35 years, SD = 11 years) for an average of 12.5 years during which 147 new cases of invasive breast cancer were diagnosed. A validated 136-item FFQ was administered at baseline and after 10 years of follow-up. The DDS (range: 11 to 55 points) positively weighted vegetables, fruit, whole cereals, nuts, coffee, low-fat dairy, fiber, PUFA; while it negatively weighted red meat, processed meats, and sugar-sweetened beverages. The DDS was categorized into tertiles. Self-reported medically diagnosed breast cancer cases were confirmed through medical records. We found a significant inverse association between the intermediate tertile of the DDS score and overall breast cancer risk (Hazard ratio, HR<sub>T2 vs. T1</sub>= 0.55; 95% CI: 0.36-0.82) and premenopausal breast cancer risk (HR<sub>T2</sub>= 0.26; 95% CI: 0.13-0.53), but not for the highest tertile. This association was stronger among women with a BMI < 25 kg/m<sup>2</sup> (p<sub>interaction</sub>: 0.029). In conclusion, moderate adherence to the DDS score was associated with a lower risk of breast cancer, especially among premenopausal women and women with a lower BMI. These findings underscore the importance of antidiabetic diet in reducing the risk of breast cancer.</p>","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142133045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ana Luz Tobaruela-Resola, Fermín I Milagro, Mariana Elorz, Alberto Benito-Boillos, José I Herrero, Paola Mogna-Peláez, Josep A Tur, J Alfredo Martínez, Itziar Abete, M Ángeles Zulet
{"title":"Circulating miR-122-5p, miR-151a-3p, miR-126-5p and miR-21-5p as potential predictive biomarkers for Metabolic Dysfunction-Associated Steatotic Liver Disease assessment.","authors":"Ana Luz Tobaruela-Resola, Fermín I Milagro, Mariana Elorz, Alberto Benito-Boillos, José I Herrero, Paola Mogna-Peláez, Josep A Tur, J Alfredo Martínez, Itziar Abete, M Ángeles Zulet","doi":"10.1007/s13105-024-01037-8","DOIUrl":"https://doi.org/10.1007/s13105-024-01037-8","url":null,"abstract":"<p><p>Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is a worldwide leading cause of liver-related associated morbidities and mortality. Currently, there is a lack of reliable non-invasive biomarkers for an accurate of MASLD. Hence, this study aimed to evidence the functional role of miRNAs as potential biomarkers for MASLD assessment. Data from 55 participants with steatosis (MASLD group) and 45 without steatosis (control group) from the Fatty Liver in Obesity (FLiO) Study (NCT03183193) were analyzed. Anthropometrics and body composition, biochemical and inflammatory markers, lifestyle factors and liver status were evaluated. Circulating miRNA levels were measured by RT-PCR. Circulating levels of miR-122-5p, miR-151a-3p, miR-126-5p and miR-21-5p were significantly increased in the MASLD group. These miRNAs were significantly associated with steatosis, liver stiffness and hepatic fat content. Logistic regression analyses revealed that miR-151a-3p or miR-21-5p in combination with leptin showed a significant diagnostic accuracy for liver stiffness obtaining an area under the curve (AUC) of 0.76 as well as miR-151a-3p in combination with glucose for hepatic fat content an AUC of 0.81. The best predictor value for steatosis was obtained by combining miR-126-5p with leptin, presenting an AUC of 0.95. Circulating miRNAs could be used as a non-invasive biomarkers for evaluating steatosis, liver stiffness and hepatic fat content, which are crucial in determining MASLD. CLINICAL TRIAL REGISTRATION: • Trial registration number: NCT03183193 ( www.clinicaltrials.gov ). • Date of registration: 12/06/2017.</p>","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141975940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Ile-Pro-Pro attenuates sympathetic activity and hypertension.","authors":"Jun-Liu Chen, Rui Ge, Xiu-Zhen Li, Yue Zhang, Wen-Yuan Hao, Na Li, Zhi-Qin Xu, Qi Chen, Yue-Hua Li, Guo-Qing Zhu, Xiao Tan","doi":"10.1007/s13105-024-01034-x","DOIUrl":"10.1007/s13105-024-01034-x","url":null,"abstract":"<p><p>Isoleucine-proline-proline (Ile-Pro-Pro, IPP) is a natural food source tripeptide that inhibits angiotensin-converting enzyme (ACE) activity. The aim of this study was to determine the central and peripheral roles of IPP in attenuating sympathetic activity, oxidative stress and hypertension. Male Sprague-Dawley rats were subjected to sham-operated surgery (Sham) or two-kidney one-clip (2K1C) surgery to induce renovascular hypertension. Renal sympathetic nerve activity and blood pressure were recorded. Bilateral microinjections of IPP to hypothalamic paraventricular nucleus (PVN) attenuated sympathetic activity (-16.1 ± 2.5%, P < 0.001) and hypertension (-8.7 ± 1.5 mmHg, P < 0.01) in 2K1C rats by inhibiting ACE activity and subsequent angiotensin II and superoxide production in the PVN. Intravenous injections of IPP also attenuated sympathetic activity (-15.1 ± 2.1%, P < 0.001) and hypertension (-16.8 ± 2.3 mmHg, P < 0.001) via inhibiting ACE activity and oxidative stress in both PVN and arteries of 2K1C rats. The duration of the effects of the intravenous IPP was longer than those of the PVN microinjection, but the sympatho-inhibitory effect of intravenous injections occurred later than that of the PVN microinjection. Intraperitoneal injection of IPP (400 pmol/day for 20 days) attenuated hypertension and vascular remodeling via inhibiting ACE activity and oxidative stress in both PVN and arteries of 2K1C rats. These results indicate that IPP attenuates hypertension and sympathetic activity by inhibiting ACE activity and oxidative stress. The sympathoinhibitory effect of peripheral IPP is mainly caused by the ACE inhibition in PVN, and the antihypertensive effect is related to the sympathoinhibition and the arterial ACE inhibition. Long-term intraperitoneal IPP therapy attenuates hypertension, oxidative stress and vascular remodeling.</p>","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":" ","pages":"585-598"},"PeriodicalIF":3.7,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141616722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Iker Gómez-García, Alfredo Fernández-Quintela, María Puy Portillo, Jenifer Trepiana
{"title":"Changes in brown adipose tissue induced by resveratrol and its analogue pterostilbene in rats fed with a high-fat high-fructose diet.","authors":"Iker Gómez-García, Alfredo Fernández-Quintela, María Puy Portillo, Jenifer Trepiana","doi":"10.1007/s13105-023-00985-x","DOIUrl":"10.1007/s13105-023-00985-x","url":null,"abstract":"<p><p>Natural bioactive compounds have attracted a great deal of attention since some of them can act as thermogenesis activators. In recent years, special interest has been placed on resveratrol and its analogue pterostilbene, a dimethylether derivative that shows higher bioavailability. The aim of the present study is to compare the effects of resveratrol and its derivative pterostilbene on the thermogenic capacity of interscapular brown adipose tissue (iBAT) in rats under a high-fat high-fructose diet. Rats were divided into four experimental groups: control, high-fat high-fructose diet (HFHF) and HFHF diet supplemented with 30 mg/kg body weight/day of pterostilbene (PT30) or resveratrol (RSV30), for eight weeks. Weights of adipose tissues, iBAT triglycerides, carnitine palmitoyltransferase 1A (CPT1A) and citrate synthase (CS) activities, protein levels of uncoupling protein 1 (UCP1), sirtuins (SIRT1 and 3), AMP-activated protein kinase (AMPK), glucose transporter (GLUT4), fatty acid synthase (FAS), nuclear respiratory factor (NRF1), hormone-sensitive lipase (HSL), adipose triglyceride lipase (ATGL), CD36 and FATP1 fatty acid transporters, peroxisome proliferator-activated receptor gamma coactivator 1 (PGC1) activation and the batokines EPDR1 and NRG4 were assessed in iBAT. The results show that some key proteins related to thermogenesis were modified by either pterostilbene or resveratrol, although the lack of effects on other crucial proteins of the thermogenic machinery suggest that these compounds were not able to stimulate this process in iBAT. Overall, these data suggest that the effects of stilbenes on brown adipose tissue thermogenic capacity depend on the metabolic status, and more precisely on the presence or absence of obesity, although further studies are needed to confirm this hypothesis.</p>","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":" ","pages":"627-637"},"PeriodicalIF":3.7,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11502549/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41236265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pauline Beaumont, Samuel Amintas, Stéphanie Krisa, Arnaud Courtois, Tristan Richard, Itziar Eseberri, Maria P Portillo
{"title":"Glucuronide metabolites of trans-ε-viniferin decrease triglycerides accumulation in an in vitro model of hepatic steatosis.","authors":"Pauline Beaumont, Samuel Amintas, Stéphanie Krisa, Arnaud Courtois, Tristan Richard, Itziar Eseberri, Maria P Portillo","doi":"10.1007/s13105-024-01035-w","DOIUrl":"10.1007/s13105-024-01035-w","url":null,"abstract":"<p><p>Trans-ε-viniferin, a resveratrol dimer found mainly in grapevine wood, has shown protective capacities against hepatic steatosis in vivo. Nevertheless, this compound is very poorly bioavailable. Thus, the aim of the present study is to determine the potential anti-steatotic properties of 1 and 10 µM of trans-ε-viniferin and its four glucuronide metabolites in AML-12 cells treated with palmitic acid as an in vitro model of hepatic steatosis. The effect of the molecules in cell viability and triglyceride accumulation, and the underlying mechanisms of action by Real-Time PCR and Western Blot were analysed, as well as the quantification of trans-ε-viniferin and the identified bioactive metabolite inside cells and their incubation media. Interestingly, we were able to determine the triglyceride-lowering property of one of the glucuronides (trans-ε-viniferin-2-glucuronide), which acts on de novo lipogenesis, fatty acid uptake and triglyceride assembly. The glucuronides of trans-ε-viniferin would therefore be partly responsible for the in vivo observed anti-steatotic properties of the parent compound.</p>","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":" ","pages":"685-696"},"PeriodicalIF":3.7,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11502592/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141860132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}