The ongoing increase in the prevalence of obesity and its comorbidities such as cardiovascular disease, type 2 diabetes (T2D) and dyslipidemia warrants discovery of novel therapeutic options for these metabolic diseases. Obesity is characterized by white adipose tissue expansion due to chronic positive energy balance as a result of excessive energy intake and/or reduced energy expenditure. Despite various efforts to prevent or reduce obesity including lifestyle and behavioral interventions, surgical weight reduction approaches and pharmacological methods, there has been limited success in significantly reducing obesity prevalence. Recent research has shown that thermogenic adipocyte (brown and beige) activation or formation, respectively, could potentially act as a therapeutic strategy to ameliorate obesity and its related disorders. This can be achieved through the ability of these thermogenic cells to enhance energy expenditure and regulate circulating levels of glucose and lipids. Thus, unraveling the molecular mechanisms behind the formation and activation of brown and beige adipocytes holds the potential for probable therapeutic paths to combat obesity. In this review, we provide a comprehensive update on the development and regulation of different adipose tissue types. We also emphasize recent interventions in harnessing therapeutic potential of thermogenic adipocytes by bioactive compounds and new pharmacological anti-obesity agents.
{"title":"Thermogenic adipose tissues: Promising therapeutic targets for metabolic diseases","authors":"Mandana Pahlavani , Kenneth Pham , Nishan Sudheera Kalupahana , Ashti Morovati , Latha Ramalingam , Hussain Abidi , Vasana Kiridana , Naima Moustaid-Moussa","doi":"10.1016/j.jnutbio.2024.109832","DOIUrl":"10.1016/j.jnutbio.2024.109832","url":null,"abstract":"<div><div>The ongoing increase in the prevalence of obesity and its comorbidities such as cardiovascular disease, type 2 diabetes (T2D) and dyslipidemia warrants discovery of novel therapeutic options for these metabolic diseases. Obesity is characterized by white adipose tissue expansion due to chronic positive energy balance as a result of excessive energy intake and/or reduced energy expenditure. Despite various efforts to prevent or reduce obesity including lifestyle and behavioral interventions, surgical weight reduction approaches and pharmacological methods, there has been limited success in significantly reducing obesity prevalence. Recent research has shown that thermogenic adipocyte (brown and beige) activation or formation, respectively, could potentially act as a therapeutic strategy to ameliorate obesity and its related disorders. This can be achieved through the ability of these thermogenic cells to enhance energy expenditure and regulate circulating levels of glucose and lipids. Thus, unraveling the molecular mechanisms behind the formation and activation of brown and beige adipocytes holds the potential for probable therapeutic paths to combat obesity. In this review, we provide a comprehensive update on the development and regulation of different adipose tissue types. We also emphasize recent interventions in harnessing therapeutic potential of thermogenic adipocytes by bioactive compounds and new pharmacological anti-obesity agents.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"137 ","pages":"Article 109832"},"PeriodicalIF":4.8,"publicationDate":"2024-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142801165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-07DOI: 10.1016/j.jnutbio.2024.109831
Youwei Zhao , Shijie Sun , Jiawen Liu , Mingzhu Zheng , Meihong Liu , Jingsheng Liu , Huimin Liu
The prevalence of hyperlipidemia is gradually increasing globally, posing a serious threat to public health. Previous studies have shown that paeoniflorin (PF) effectively improved abnormal lipid metabolism in atherosclerotic mice. However, the anti-hyperlipidemia effect and potential mechanism of paeoniflorin remain unclear. The gut microbiota (GM) is closely related to hyperlipidemia. This study was aimed to investigate effects of PF on improving the health of high-fat diet (HFD)-induced hyperlipidemic mice by modulating GM. A hyperlipidemic mouse model was established using an HFD, and the hypolipidemic effect of PF was detected in vivo. Besides16S ribosomal RNA sequencing and SCFAs metabolic analysis were performed to explore the lipid-lowering mechanism of PF. Importantly, fecal microbiota transplantation (FMT) experiments were conducted to verify the lipid-lowering mechanism of PF. The results showed that PF significantly inhibited the development of hyperlipidemia, reduced serum lipid and inflammatory cytokine levels, and improved liver steatosis. In addition, 16S rRNA sequencing revealed that PF treatment significantly increased the relative abundance of Lactobacillus, Coprococcus, Blautia, Roseburia, and Bacteroides while reducing the relative abundance of Prevotella. Meanwhile, the results of targeted metabolomics indicate that PF therapy can effectively restore butyric acid and propionic acid levels in the intestine. The FMT experiments further demonstrated that PF improved hyperlipidemia by regulating GM and its metabolites. The above results provide a valuable theoretical basis for the development and application of PF as a functional food for hyperlipidemia.
{"title":"Investigation of the protective mechanism of paeoniflorin against hyperlipidemia by an integrated metabolomics and gut microbiota strategy","authors":"Youwei Zhao , Shijie Sun , Jiawen Liu , Mingzhu Zheng , Meihong Liu , Jingsheng Liu , Huimin Liu","doi":"10.1016/j.jnutbio.2024.109831","DOIUrl":"10.1016/j.jnutbio.2024.109831","url":null,"abstract":"<div><div>The prevalence of hyperlipidemia is gradually increasing globally, posing a serious threat to public health. Previous studies have shown that paeoniflorin (PF) effectively improved abnormal lipid metabolism in atherosclerotic mice. However, the anti-hyperlipidemia effect and potential mechanism of paeoniflorin remain unclear. The gut microbiota (GM) is closely related to hyperlipidemia. This study was aimed to investigate effects of PF on improving the health of high-fat diet (HFD)-induced hyperlipidemic mice by modulating GM. A hyperlipidemic mouse model was established using an HFD, and the hypolipidemic effect of PF was detected in vivo. Besides16S ribosomal RNA sequencing and SCFAs metabolic analysis were performed to explore the lipid-lowering mechanism of PF. Importantly, fecal microbiota transplantation (FMT) experiments were conducted to verify the lipid-lowering mechanism of PF. The results showed that PF significantly inhibited the development of hyperlipidemia, reduced serum lipid and inflammatory cytokine levels, and improved liver steatosis. In addition, 16S rRNA sequencing revealed that PF treatment significantly increased the relative abundance of <em>Lactobacillus, Coprococcus, Blautia, Roseburia</em>, and <em>Bacteroides</em> while reducing the relative abundance of <em>Prevotella</em>. Meanwhile, the results of targeted metabolomics indicate that PF therapy can effectively restore butyric acid and propionic acid levels in the intestine. The FMT experiments further demonstrated that PF improved hyperlipidemia by regulating GM and its metabolites. The above results provide a valuable theoretical basis for the development and application of PF as a functional food for hyperlipidemia.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"137 ","pages":"Article 109831"},"PeriodicalIF":4.8,"publicationDate":"2024-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142801164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Poor intrauterine environments increase the prevalence of chronic metabolic diseases in offspring, whereas maternal exercise is an effective measure to break this vicious intergenerational cycle. Placenta is increasingly being studied to explore its role in maternal-fetal metabolic cross-talk. The association between placental miRNA and offspring development trajectories has been established, yet the specific role and mechanism thereof in maternal exercise-induced metabolic protection remain elusive. Here, C57BL/6 female mice were subjected to either a normal control or a high-fat diet (HFD), half of the HFD-fed dams were housed with voluntary wheel running for 3 weeks before and during gestation. At embryonic day 18.5, we sacrificed parturient mice and then conducted miRNA-seq, transcriptomic, and metabolomic profiling of the placenta. Our data revealed that maternal HFD resulted in significant alterations in both miRNA and gene expressions, as well as metabolic pathways of the placenta, whereas prenatal exercise negated these perturbations. The common differentially expressed transcripts among three groups were enriched in multiple critical pathways involving energy expenditure, signal transduction, and fetal development. Through integrated analysis of multiomics data, we speculated that maternal exercise reversed the suppression of miR-495-5p induced by HFD, thereby inhibiting miR-495-5p-targeted Snx7 and modulating kynurenic acid production. These datasets provided novel mechanistic insight into how maternal exercise positively affects the metabolic homeostasis of offspring. The discovered important miRNAs, mRNAs, and metabolites could be promising predictive and therapeutic targets for protecting offspring metabolic health.
{"title":"Maternal exercise programs placental miR-495-5p-mediated Snx7 expression and kynurenic acid metabolic pathway induced by prenatal high-fat diet: Based on miRNA-seq, transcriptomics, and metabolomics","authors":"Shunhua Li , Liyuan Zhou , Jing Ren , Qian Zhang , Xinhua Xiao","doi":"10.1016/j.jnutbio.2024.109830","DOIUrl":"10.1016/j.jnutbio.2024.109830","url":null,"abstract":"<div><div>Poor intrauterine environments increase the prevalence of chronic metabolic diseases in offspring, whereas maternal exercise is an effective measure to break this vicious intergenerational cycle. Placenta is increasingly being studied to explore its role in maternal-fetal metabolic cross-talk. The association between placental miRNA and offspring development trajectories has been established, yet the specific role and mechanism thereof in maternal exercise-induced metabolic protection remain elusive. Here, C57BL/6 female mice were subjected to either a normal control or a high-fat diet (HFD), half of the HFD-fed dams were housed with voluntary wheel running for 3 weeks before and during gestation. At embryonic day 18.5, we sacrificed parturient mice and then conducted miRNA-seq, transcriptomic, and metabolomic profiling of the placenta. Our data revealed that maternal HFD resulted in significant alterations in both miRNA and gene expressions, as well as metabolic pathways of the placenta, whereas prenatal exercise negated these perturbations. The common differentially expressed transcripts among three groups were enriched in multiple critical pathways involving energy expenditure, signal transduction, and fetal development. Through integrated analysis of multiomics data, we speculated that maternal exercise reversed the suppression of miR-495-5p induced by HFD, thereby inhibiting miR-495-5p-targeted <em>Snx7</em> and modulating kynurenic acid production. These datasets provided novel mechanistic insight into how maternal exercise positively affects the metabolic homeostasis of offspring. The discovered important miRNAs, mRNAs, and metabolites could be promising predictive and therapeutic targets for protecting offspring metabolic health.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"137 ","pages":"Article 109830"},"PeriodicalIF":4.8,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-05DOI: 10.1016/j.jnutbio.2024.109822
Ruoshi Zhang , Jing Sun , Yingjie Wang , Hao Yu , Shenao Wang , Xingjun Feng
The aim of this study was to investigate the ameliorative effects of pterostilbene (PTE), a polyphenolic compound, on stress-induced lipid metabolic disorders in the liver of broiler chickens. Six hundred healthy, 1-day-old Arbor Acres with similar weight were randomly assigned to five groups, each consisting of eight replicates with 15 broilers per replicate. The groups included: a control group (fed a basal diet), and four groups treated with corticosterone (CORT) at varying dietary levels of PTE supplementation: CORT (0 mg/kg PTE), CORT-PT200 (200 mg/kg PTE), CORT-PT400 (400 mg/kg PTE), and CORT-PT600 (600 mg/kg PTE). The results indicated that PTE administration to corticosterone (CORT)-injected broilers significantly improved weight gain, reduced liver index, and lowered the elevation of serum aspartate aminotransferase, gamma-glutamyl transferase, glucose, total cholesterol, triglycerides, and lipoprotein cholesterol concentrations induced by CORT injection (P<.05), but had no significant effect on serum CORT concentration (P>.05). PTE also significantly reduced the increased rate of abdominal fat deposition induced by CORT, decreased the average size of adipocytes, and downregulated the expression of the FAS gene (P<.05). It reversed the increase in liver total cholesterol, triglycerides, lipoprotein cholesterol, and non-esterified fatty acids content induced by CORT (P<.05). PTE had no significant effect on the expression of the glucocorticoid receptor (P>.05), but significantly upregulated the protein expression of Sirt1 and p-AMPK (P<.05), promoted the expression of lipid autophagy genes MAP1LC3B and lipolytic genes LPL, but inhibited the expression of fatty acid synthesis genes SREBP-1c, ACC, and SCD (P<.05). The addition of PTE to the diet alleviated CORT-induced oxidative stress and inflammation by enhancing T-SOD and GSH-Px activities, reducing MDA content, inhibiting p-NF-κB p65 and NLRP3 expression and the release of TNF-α and IL-1β in the serum, and increasing IL-4 content (P<.05). Overall, dietary PTE effectively regulates lipid metabolism and antioxidant status, offering a potential strategy to mitigate stress-induced metabolic disruptions in broilers.
{"title":"Ameliorative effect of phenolic compound-pterostilbene on corticosterone-induced hepatic lipid metabolic disorder in broilers","authors":"Ruoshi Zhang , Jing Sun , Yingjie Wang , Hao Yu , Shenao Wang , Xingjun Feng","doi":"10.1016/j.jnutbio.2024.109822","DOIUrl":"10.1016/j.jnutbio.2024.109822","url":null,"abstract":"<div><div>The aim of this study was to investigate the ameliorative effects of pterostilbene (PTE), a polyphenolic compound, on stress-induced lipid metabolic disorders in the liver of broiler chickens. Six hundred healthy, 1-day-old Arbor Acres with similar weight were randomly assigned to five groups, each consisting of eight replicates with 15 broilers per replicate. The groups included: a control group (fed a basal diet), and four groups treated with corticosterone (CORT) at varying dietary levels of PTE supplementation: CORT (0 mg/kg PTE), CORT-PT200 (200 mg/kg PTE), CORT-PT400 (400 mg/kg PTE), and CORT-PT600 (600 mg/kg PTE). The results indicated that PTE administration to corticosterone (CORT)-injected broilers significantly improved weight gain, reduced liver index, and lowered the elevation of serum aspartate aminotransferase, gamma-glutamyl transferase, glucose, total cholesterol, triglycerides, and lipoprotein cholesterol concentrations induced by CORT injection (<em>P<.</em>05), but had no significant effect on serum CORT concentration (<em>P>.</em>05). PTE also significantly reduced the increased rate of abdominal fat deposition induced by CORT, decreased the average size of adipocytes, and downregulated the expression of the FAS gene (<em>P<.</em>05). It reversed the increase in liver total cholesterol, triglycerides, lipoprotein cholesterol, and non-esterified fatty acids content induced by CORT (<em>P<.</em>05). PTE had no significant effect on the expression of the glucocorticoid receptor (<em>P>.</em>05), but significantly upregulated the protein expression of Sirt1 and p-AMPK (<em>P<.</em>05), promoted the expression of lipid autophagy genes MAP1LC3B and lipolytic genes LPL, but inhibited the expression of fatty acid synthesis genes SREBP-1c, ACC, and SCD (<em>P<.</em>05). The addition of PTE to the diet alleviated CORT-induced oxidative stress and inflammation by enhancing T-SOD and GSH-Px activities, reducing MDA content, inhibiting p-NF-κB p65 and NLRP3 expression and the release of TNF-α and IL-1β in the serum, and increasing IL-4 content (<em>P<.</em>05). Overall, dietary PTE effectively regulates lipid metabolism and antioxidant status, offering a potential strategy to mitigate stress-induced metabolic disruptions in broilers.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"137 ","pages":"Article 109822"},"PeriodicalIF":4.8,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-29DOI: 10.1016/j.jnutbio.2024.109814
Vincent Ciesielski , Thomas Guerbette , Léa Fret , Mélodie Succar , Youenn Launay , Patrice Dahirel , Philippe Legrand , Manuel Vlach , Sophie Blat , Vincent Rioux
Pentadecanoic acid (C15:0) is a saturated odd-chain fatty acid (OCFA), mainly found in dairy products. Its physiological and nutritional effects are still unknown, yet some recent evidences suggest it might be beneficial to human health. Moreover, pentadecanoic acid has recently been suspected of having essential roles in humans, although the mechanisms are not described. We therefore questioned the potential essentiality of this fatty acid (FA). We investigated in vivo the effect of a C15:0 supplementation on essential fatty acid (EFA) deficient Wistar rats. Female rats were fed an EFA-deficient diet 2 weeks before mating, during pregnancy and lactation. Weaned pups were fed the EFA-deficient diet or were switched to a diet supplemented with C15:0 or linoleic acid (LA) for 11 weeks. A control group was fed with EFA during the whole study. Since linoleic acid deficiency is known to induce growth delay, weights were measured throughout the experiment and FA content in collected tissues were analyzed to evaluate biochemical markers of the deficiency. As expected, EFA-deficient rats showed growth retardation, compared to control rats. Supplementation of C15:0 at weaning increased early growth rate compared to deficient animals, as also did the supplementation of C18:2 n-6. Furthermore, the supplementation of C15:0 in the diet of EFA-deficient animals induced the previously undescribed synthesis of odd-chain PUFAs of the n-8 family (C19:3, C21:3 and C21:4 n-8). These results suggest dietary C15:0 might counteract EFA induced growth retardation, possibly through the synthesis of odd-chain n-8 PUFAs, yet mechanisms are to be deciphered for further validation.
{"title":"Dietary pentadecanoic acid supplementation at weaning in essential fatty acid-deficient rats shed light on the new family of odd-chain n-8 PUFAs","authors":"Vincent Ciesielski , Thomas Guerbette , Léa Fret , Mélodie Succar , Youenn Launay , Patrice Dahirel , Philippe Legrand , Manuel Vlach , Sophie Blat , Vincent Rioux","doi":"10.1016/j.jnutbio.2024.109814","DOIUrl":"10.1016/j.jnutbio.2024.109814","url":null,"abstract":"<div><div>Pentadecanoic acid (C15:0) is a saturated odd-chain fatty acid (OCFA), mainly found in dairy products. Its physiological and nutritional effects are still unknown, yet some recent evidences suggest it might be beneficial to human health. Moreover, pentadecanoic acid has recently been suspected of having essential roles in humans, although the mechanisms are not described. We therefore questioned the potential essentiality of this fatty acid (FA). We investigated <em>in vivo</em> the effect of a C15:0 supplementation on essential fatty acid (EFA) deficient Wistar rats. Female rats were fed an EFA-deficient diet 2 weeks before mating, during pregnancy and lactation. Weaned pups were fed the EFA-deficient diet or were switched to a diet supplemented with C15:0 or linoleic acid (LA) for 11 weeks. A control group was fed with EFA during the whole study. Since linoleic acid deficiency is known to induce growth delay, weights were measured throughout the experiment and FA content in collected tissues were analyzed to evaluate biochemical markers of the deficiency. As expected, EFA-deficient rats showed growth retardation, compared to control rats. Supplementation of C15:0 at weaning increased early growth rate compared to deficient animals, as also did the supplementation of C18:2 n-6. Furthermore, the supplementation of C15:0 in the diet of EFA-deficient animals induced the previously undescribed synthesis of odd-chain PUFAs of the n-8 family (C19:3, C21:3 and C21:4 n-8). These results suggest dietary C15:0 might counteract EFA induced growth retardation, possibly through the synthesis of odd-chain n-8 PUFAs, yet mechanisms are to be deciphered for further validation.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"137 ","pages":"Article 109814"},"PeriodicalIF":4.8,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142769875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-26DOI: 10.1016/j.jnutbio.2024.109813
Ziyi Chen , Shu Liu , Fengrui Song , Zong Hou , Hui Zhou , Yuting Fan , Rongjin Wang , Zhongying Liu
Alzheimer's disease (AD) is a complex neurodegenerative disease. Nervonic acid is a component of breast milk and is also found in fish oil and specific vegetable oils. Studies have shown that nervonic acid is essential for the development of the human nervous system. In this study, Morris water maze (MWM) test and pathological analysis showed that nervonic acid could improve cognitive deficits and brain nerve damage in AD rats. Then, through sequencing, we found that nervonic acid increased the abundance of beneficial bacteria such as Lactobacillus and Bacteroides, and decreased the abundance of Pseudomonadaceae_Pseudomonas. Not only that, nervonic acid also regulates the production of short-chain fatty acids (SCFA) and the levels of 29 fecal metabolites, and affects the metabolism of linoleic acid, α-linolenic acid, arachidonic acid, and sphingolipid. Finally, we verified the regulatory effect of nervonic acid on metabolic enzyme activity.
{"title":"Integrated metabolome and microbiome strategy reveals the therapeutic effect of nervonic acid on Alzheimer's disease rats","authors":"Ziyi Chen , Shu Liu , Fengrui Song , Zong Hou , Hui Zhou , Yuting Fan , Rongjin Wang , Zhongying Liu","doi":"10.1016/j.jnutbio.2024.109813","DOIUrl":"10.1016/j.jnutbio.2024.109813","url":null,"abstract":"<div><div>Alzheimer's disease (AD) is a complex neurodegenerative disease. Nervonic acid is a component of breast milk and is also found in fish oil and specific vegetable oils. Studies have shown that nervonic acid is essential for the development of the human nervous system. In this study, Morris water maze (MWM) test and pathological analysis showed that nervonic acid could improve cognitive deficits and brain nerve damage in AD rats. Then, through sequencing, we found that nervonic acid increased the abundance of beneficial bacteria such as <em>Lactobacillus</em> and <em>Bacteroides</em>, and decreased the abundance of <em>Pseudomonadaceae_Pseudomonas</em>. Not only that, nervonic acid also regulates the production of short-chain fatty acids (SCFA) and the levels of 29 fecal metabolites, and affects the metabolism of linoleic acid, α-linolenic acid, arachidonic acid, and sphingolipid. Finally, we verified the regulatory effect of nervonic acid on metabolic enzyme activity.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"137 ","pages":"Article 109813"},"PeriodicalIF":4.8,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142739824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-26DOI: 10.1016/j.jnutbio.2024.109812
Ying Zhang , Xin Zhao , Na Zhao , Yan Song , Zixuan Zhang , Xinbao Zhang , Haohao Meng , Xiru Wang , Le Shan , Wanqi Zhang , Zhongna Sang
Iodine is critical for thyroid hormone synthesis and developmental programming in the first 1,000 days of life. The effect of maternal iodine on milk protein secretion remains unknown. We aimed to explore the effect of long-term maternal iodine deficiency and excess on milk protein secretion in lactating rats and its mechanisms preliminarily. Animal models of iodine deficiency and excess were generated by treating Wistar rats a low-iodine diet and deionized water with different potassium iodide concentrations from reproductive age to lactation. Under iodine deficiency, CSN2 and α-LA secretion of milk was inhibited in early and mid-lactation, respectively, and the inhibition of milk CSN2 and α-LA secretion weakened in late lactation. Under iodine excess, milk CSN2 secretion was inhibited in early lactation, and the inhibition of milk CSN2 and α-LA secretion was more pronounced in late lactation. Under iodine deficiency and excess, the concentrations of CSN2 and α-LA and protein expression levels of THRα1, THRβ1, and PRLR in the mammary gland decreased. These results demonstrate the negative impact of long-term maternal iodine malnutrition on milk protein secretion.
{"title":"Long-term iodine deficiency and excess inhibit β-casein and α-lactalbumin secretion of milk in lactating rats","authors":"Ying Zhang , Xin Zhao , Na Zhao , Yan Song , Zixuan Zhang , Xinbao Zhang , Haohao Meng , Xiru Wang , Le Shan , Wanqi Zhang , Zhongna Sang","doi":"10.1016/j.jnutbio.2024.109812","DOIUrl":"10.1016/j.jnutbio.2024.109812","url":null,"abstract":"<div><div>Iodine is critical for thyroid hormone synthesis and developmental programming in the first 1,000 days of life. The effect of maternal iodine on milk protein secretion remains unknown. We aimed to explore the effect of long-term maternal iodine deficiency and excess on milk protein secretion in lactating rats and its mechanisms preliminarily. Animal models of iodine deficiency and excess were generated by treating Wistar rats a low-iodine diet and deionized water with different potassium iodide concentrations from reproductive age to lactation. Under iodine deficiency, CSN2 and α-LA secretion of milk was inhibited in early and mid-lactation, respectively, and the inhibition of milk CSN2 and α-LA secretion weakened in late lactation. Under iodine excess, milk CSN2 secretion was inhibited in early lactation, and the inhibition of milk CSN2 and α-LA secretion was more pronounced in late lactation. Under iodine deficiency and excess, the concentrations of CSN2 and α-LA and protein expression levels of THRα1, THRβ1, and PRLR in the mammary gland decreased. These results demonstrate the negative impact of long-term maternal iodine malnutrition on milk protein secretion.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"137 ","pages":"Article 109812"},"PeriodicalIF":4.8,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142738804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Impaired wound healing from diabetes mellitus (DM) causes lower limb amputations, posing clinical, social, and economic issues. Hypoxia and advanced glycation end products cause autophagy and apoptosis dysregulation, which delays wound healing. The study will test systemic and topical Nicotinamide Riboside (NR) and Resveratrol (RSV) for the capacity to modulate autophagy and apoptosis via the SIRT-1-FOXO1 pathway and improve diabetic wound healing. About 54 male Sprague-Dawley rats were separated into control, diabetic (T1D), T1D-Gel-Base, T1D-NR, T1D-RSV, and T1D-NR+RSV groups. Rats were gavaged with 50 mg/kg/day RSV and 300 mg/kg/day NR for 5 weeks before having their wounds topically treated with 5% NR and RSV gel for 15 days after diabetes induction. Biochemical, histomorphometric, and stereological assays were conducted. The mRNA expressions of SIRT-1, FOXO1, VEGF, BAX, Cas3, Bcl-2, Beclin1, LC3IIβ, P62, and ATG5 were examined by qRT-PCR. NR and RSV improved diabetic rat wound closure. Diabetic rats treated with NR and RSV had significantly higher LC3IIβ, VEGEF, Bcl-2, and SIRT-1 mRNA levels. Bcl-2, p62, and ATG5 were regulated whereas BAX and Cas 3 were reduced. Stereological investigations showed epidermal, dermal, collagen bundle, vascular, and fibroblast density enhancements. This study highlights the potential of NR and RSV, acting as SIRT-1 activators, in improving diabetic wound healing by regulating SIRT-1-FOXO1-mediated autophagy and apoptosis. These findings offer valuable insights for developing targeted strategies to enhance diabetic wound healing. The combination of NR and RSV showed promising effects, suggesting a potential therapeutic approach for improving diabetic wound healing.
{"title":"Enhancing wound healing via modulation of autophagy-induced apoptosis: the role of nicotinamide riboside and resveratrol in streptozotocin-treated diabetic rat","authors":"Morvarid Siri , Mohammad Hasan Maleki , Seyed Mohammadmahdi Meybodi , Seyed Amirhossein Mazhari , Fatemeh Ghaderi Saviri , Amirreza Dehghanian , Maryam Naseh , Nafiseh Esmaeili , Sanaz Dastghaib , Zeinab Aryanian","doi":"10.1016/j.jnutbio.2024.109811","DOIUrl":"10.1016/j.jnutbio.2024.109811","url":null,"abstract":"<div><div>Impaired wound healing from diabetes mellitus (DM) causes lower limb amputations, posing clinical, social, and economic issues. Hypoxia and advanced glycation end products cause autophagy and apoptosis dysregulation, which delays wound healing. The study will test systemic and topical Nicotinamide Riboside (NR) and Resveratrol (RSV) for the capacity to modulate autophagy and apoptosis via the SIRT-1-FOXO1 pathway and improve diabetic wound healing. About 54 male Sprague-Dawley rats were separated into control, diabetic (T1D), T1D-Gel-Base, T1D-NR, T1D-RSV, and T1D-NR+RSV groups. Rats were gavaged with 50 mg/kg/day RSV and 300 mg/kg/day NR for 5 weeks before having their wounds topically treated with 5% NR and RSV gel for 15 days after diabetes induction. Biochemical, histomorphometric, and stereological assays were conducted. The mRNA expressions of <em>SIRT-1, FOXO1, VEGF, BAX, Cas3, Bcl-2, Beclin1, LC3IIβ, P62</em>, and <em>ATG5</em> were examined by qRT-PCR. NR and RSV improved diabetic rat wound closure. Diabetic rats treated with NR and RSV had significantly higher <em>LC3IIβ, VEGEF, Bcl-2</em>, and <em>SIRT-1</em> mRNA levels. <em>Bcl-2, p62</em>, and <em>ATG5</em> were regulated whereas <em>BAX</em> and <em>Cas 3</em> were reduced. Stereological investigations showed epidermal, dermal, collagen bundle, vascular, and fibroblast density enhancements. This study highlights the potential of NR and RSV, acting as SIRT-1 activators, in improving diabetic wound healing by regulating SIRT-1-FOXO1-mediated autophagy and apoptosis. These findings offer valuable insights for developing targeted strategies to enhance diabetic wound healing. The combination of NR and RSV showed promising effects, suggesting a potential therapeutic approach for improving diabetic wound healing.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"137 ","pages":"Article 109811"},"PeriodicalIF":4.8,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142693236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-19DOI: 10.1016/j.jnutbio.2024.109805
Aline Rosignoli da Conceição , Josefina Bressan , Marta Cuervo , Maria Luisa Mansego , J. Alfredo Martínez , José Ignacio Riezu-Boj , Fermín I. Milagro
Epigenetic mechanisms, which can be modulated by dietary factors, have been proposed as a possible factor in understanding interindividual differences in disease susceptibility. We aimed to determine the relationships between DNA methylation (DNAm), diet quality, and metabolic health in Spanish individuals. This is a transversal study encompassing 337 male and female participants in the Obekit study. Diet quality was assessed using a validated semiquantitative food frequency questionnaire and seven previously established scores: overall, healthy and unhealthy Plant-Based Diet Index (PDI, hPDI and uPDI, respectively), dietary diversity score (DDS), unprocessed/minimally processed foods (MPF) and ultra-processed foods (UPF) consumption and Mediterranean diet (MD) score. DNAm was analyzed in white blood cells using the Infinium MethylationEPIC v1.0 BeadChip kit. After filtering by a variance >0.36, we have worked with 5,261 CpG sites. We found four false discovery rate (FDR)-significant correlations between nutrients and CpGs sites: cg00167275 (GLUD1) correlated with alcohol, cg05218090 with folic acid, cg16682935 (PAPSS2) with selenium, and cg09821790 (SLC7A6) with fish food. One differentially methylated region (DMR) located at zinc finger protein gene 57 (ZFP57) was closely related to obesity and specific nutrients, food groups, and diet quality indices. The regression models of diet quality based on DNAm demonstrated that the most predictive values were when UPF and hPDI were considered. Also, UPF and hPDI were the best indices for predicting the main cardiometabolic risk factors. Our finding suggests that specific nutrients and diet quality indices may influence the degree of DNAm and putatively, the metabolic health in Spanish individuals.
{"title":"Relationship between blood DNA methylation, diet quality indices and metabolic health: Data from Obekit study","authors":"Aline Rosignoli da Conceição , Josefina Bressan , Marta Cuervo , Maria Luisa Mansego , J. Alfredo Martínez , José Ignacio Riezu-Boj , Fermín I. Milagro","doi":"10.1016/j.jnutbio.2024.109805","DOIUrl":"10.1016/j.jnutbio.2024.109805","url":null,"abstract":"<div><div>Epigenetic mechanisms, which can be modulated by dietary factors, have been proposed as a possible factor in understanding interindividual differences in disease susceptibility. We aimed to determine the relationships between DNA methylation (DNAm), diet quality, and metabolic health in Spanish individuals. This is a transversal study encompassing 337 male and female participants in the Obekit study. Diet quality was assessed using a validated semiquantitative food frequency questionnaire and seven previously established scores: overall, healthy and unhealthy Plant-Based Diet Index (PDI, hPDI and uPDI, respectively), dietary diversity score (DDS), unprocessed/minimally processed foods (MPF) and ultra-processed foods (UPF) consumption and Mediterranean diet (MD) score. DNAm was analyzed in white blood cells using the Infinium MethylationEPIC v1.0 BeadChip kit. After filtering by a variance >0.36, we have worked with 5,261 CpG sites. We found four false discovery rate (FDR)-significant correlations between nutrients and CpGs sites: cg00167275 (<em>GLUD1</em>) correlated with alcohol, cg05218090 with folic acid, cg16682935 (<em>PAPSS2</em>) with selenium, and cg09821790 (<em>SLC7A6</em>) with fish food. One differentially methylated region (DMR) located at zinc finger protein gene 57 (<em>ZFP57</em>) was closely related to obesity and specific nutrients, food groups, and diet quality indices. The regression models of diet quality based on DNAm demonstrated that the most predictive values were when UPF and hPDI were considered. Also, UPF and hPDI were the best indices for predicting the main cardiometabolic risk factors. Our finding suggests that specific nutrients and diet quality indices may influence the degree of DNAm and putatively, the metabolic health in Spanish individuals.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"136 ","pages":"Article 109805"},"PeriodicalIF":4.8,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142687245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-19DOI: 10.1016/j.jnutbio.2024.109808
Rong Liu , Yi Zhang , Min Liu , Zhiyin Shang , Shu Song , Yajun Zhang , Yingqun Zhou , Chuantao Tu
Isoliquiritigenin (ISL), a flavonoid derived from licorice root, has diverse biological and pharmacological properties. This study aimed to investigate the hepatoprotective effects and mechanism of action of ISL on the pathogenesis of metabolic dysfunction-associated steatohepatitis (MASH). C57BL/6 mice fed a chow diet or choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) received ISL (10 mg/kg) or vehicle daily via oral administration. To further explore the mechanism of ISL in MASH pathogenesis, AML12 cells were exposed to palmitic acid (PA) as an in vitro model of lipid toxicity. The results showed that, compared with vehicle-treated mice, ISL treatment alleviated liver injury, steatosis, inflammation, and fibrosis in MASH mice. Moreover, ISL treatment reduced the recruitment of CD68+ macrophages and activated hepatic stellate cells (HSCs) in MASH livers. In vitro experiments showed that ISL reduced lipid accumulation and mitigated inflammatory responses in PA-induced AML12 cells. Notably, RNA-sequencing analyses revealed that the anti-MASH effect of ISL enhanced autophagy via the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway. This was further validated by assessing autophagy markers in both MASH liver tissues and PA-stimulated AML12 cells in vitro. Additionally, molecular docking analysis demonstrated that the target proteins of ISL exhibited strong binding affinity to PIK3 isoforms. In conclusion, our findings highlight that ISL mitigates MASH and fibrosis in mice by promoting autophagy through the PI3K/Akt/mTOR signaling pathway, providing reliable evidence to support further studies on MASH in humans.
异桔梗甙元（ISL）是从甘草根中提取的一种黄酮类化合物，具有多种生物学和药理学特性。本研究旨在探讨 ISL 对代谢功能障碍相关性脂肪性肝炎（MASH）发病机制的保肝作用及其作用机制。C57BL/6小鼠以饲料或胆碱缺乏、L-氨基酸定义的高脂饲料（CDAHFD）为食谱，每天口服ISL（10 mg/kg）或载体。为了进一步探讨ISL在MASH发病机制中的作用，研究人员将AML12细胞暴露于棕榈酸（PA）作为脂质毒性的体外模型。结果表明，与用药物治疗的小鼠相比，ISL治疗减轻了MASH小鼠的肝损伤、脂肪变性、炎症和纤维化。此外，ISL还能减少MASH肝脏中CD68+巨噬细胞和活化的肝星状细胞（HSCs）的招募。体外实验表明，ISL可减少脂质积累，减轻PA诱导的AML12细胞的炎症反应。值得注意的是，RNA序列分析表明，ISL的抗MASH作用通过磷脂酰肌醇3-激酶（PI3K）/蛋白激酶B（AKT）/哺乳动物雷帕霉素靶标（mTOR）信号通路增强了自噬。通过评估 MASH 肝组织和 PA 刺激的 AML12 细胞体外自噬标记物，进一步验证了这一点。此外，分子对接分析表明，ISL的靶蛋白与PIK3同工酶具有很强的结合亲和力。总之，我们的研究结果突出表明，ISL通过PI3K/Akt/mTOR信号通路促进自噬，从而减轻小鼠的MASH和肝纤维化，为进一步研究人类MASH提供了可靠的证据。
{"title":"Natural molecule isoliquiritigenin mitigates MASH and liver fibrosis in mice by promoting autophagy through the PI3K/Akt signaling pathway","authors":"Rong Liu , Yi Zhang , Min Liu , Zhiyin Shang , Shu Song , Yajun Zhang , Yingqun Zhou , Chuantao Tu","doi":"10.1016/j.jnutbio.2024.109808","DOIUrl":"10.1016/j.jnutbio.2024.109808","url":null,"abstract":"<div><div>Isoliquiritigenin (ISL), a flavonoid derived from licorice root, has diverse biological and pharmacological properties. This study aimed to investigate the hepatoprotective effects and mechanism of action of ISL on the pathogenesis of metabolic dysfunction-associated steatohepatitis (MASH). C57BL/6 mice fed a chow diet or choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) received ISL (10 mg/kg) or vehicle daily via oral administration. To further explore the mechanism of ISL in MASH pathogenesis, AML12 cells were exposed to palmitic acid (PA) as an <em>in vitro</em> model of lipid toxicity. The results showed that, compared with vehicle-treated mice, ISL treatment alleviated liver injury, steatosis, inflammation, and fibrosis in MASH mice. Moreover, ISL treatment reduced the recruitment of CD68<sup>+</sup> macrophages and activated hepatic stellate cells (HSCs) in MASH livers. <em>In vitro</em> experiments showed that ISL reduced lipid accumulation and mitigated inflammatory responses in PA-induced AML12 cells. Notably, RNA-sequencing analyses revealed that the anti-MASH effect of ISL enhanced autophagy via the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway. This was further validated by assessing autophagy markers in both MASH liver tissues and PA-stimulated AML12 cells in vitro. Additionally, molecular docking analysis demonstrated that the target proteins of ISL exhibited strong binding affinity to PIK3 isoforms. In conclusion, our findings highlight that ISL mitigates MASH and fibrosis in mice by promoting autophagy through the PI3K/Akt/mTOR signaling pathway, providing reliable evidence to support further studies on MASH in humans.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"136 ","pages":"Article 109808"},"PeriodicalIF":4.8,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142687188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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