Pub Date : 2024-09-05DOI: 10.1016/j.jnutbio.2024.109750
{"title":"Commentary—research diets and reproducible results in rodent models","authors":"","doi":"10.1016/j.jnutbio.2024.109750","DOIUrl":"10.1016/j.jnutbio.2024.109750","url":null,"abstract":"","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145816","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}
Aging causes changes in liver morphophysiology, altering hepatocyte morphology and organ function. Due to its antioxidant and anti-inflammatory properties, coconut oil has been used as a therapeutic agent in diets, in an attempt to attenuate alterations in the liver naturally caused by aging. Herein, we evaluated the effects of coconut oil consumption during aging on Mongolian gerbil liver morphophysiology. The animals were divided into three experimental groups: the gerbils in the Adult Control Group (AC) were euthanized at 3 months of age, the gerbils in the Old Control Group (OC) at 15 months of age, and the gerbils in the Coconut Oil Group (CO) received 0.1 ml/day of coconut oil for 12 months and were euthanized at 15 months of age. Prolonged consumption of coconut oil during aging prevented the animals and the liver from gaining mass. However, the other results showed that coconut oil intensified the morphophysiological alterations of aging, promoting an increase in the hepatocyte cytoplasm and nuclei. In addition, an increase in blood vessels, reticular fibers, lipid droplets, and lipofuscin granules were observed in the CO group. Finally, the results also demonstrated that coconut oil promotes an increase in lipid peroxidation, indicated by an increase in MDA levels. We therefore conclude that coconut oil has the potential to intensify the morphophysiological alterations that occur in the liver during aging.
衰老会导致肝脏形态生理学发生变化,改变肝细胞形态和器官功能。由于椰子油具有抗氧化和抗炎特性,它已被用作膳食中的一种治疗剂,试图减轻衰老自然引起的肝脏变化。在此,我们评估了衰老过程中食用椰子油对蒙古沙鼠肝脏形态生理学的影响。动物被分为三个实验组:成年对照组(AC)的沙鼠在3月龄时安乐死,老年对照组(OC)的沙鼠在15月龄时安乐死,椰子油组(CO)的沙鼠在12个月内每天摄入0.1毫升椰子油,并在15月龄时安乐死。在衰老过程中长期食用椰子油可防止动物和肝脏增重。然而,其他结果显示,椰子油加剧了衰老的形态生理变化,促进了肝细胞细胞质和细胞核的增加。此外,在 CO 组中还观察到血管、网状纤维、脂滴和脂褐素颗粒的增加。最后,研究结果还表明,椰子油会促进脂质过氧化的增加,表现为 MDA 水平的增加。因此,我们得出结论,椰子油有可能加剧肝脏在衰老过程中发生的形态生理变化。
{"title":"Coconut oil affects aging-related changes in Mongolian gerbil liver morphophysiology.","authors":"Vitor Grigio, Luiz Henrique Alves Guerra, Stella Bicalho Silva, Mariella Bontempo Freitas, Sebastião Roberto Taboga, Patrícia Simone Leite Vilamaior","doi":"10.1016/j.jnutbio.2024.109749","DOIUrl":"https://doi.org/10.1016/j.jnutbio.2024.109749","url":null,"abstract":"<p><p>Aging causes changes in liver morphophysiology, altering hepatocyte morphology and organ function. Due to its antioxidant and anti-inflammatory properties, coconut oil has been used as a therapeutic agent in diets, in an attempt to attenuate alterations in the liver naturally caused by aging. Herein, we evaluated the effects of coconut oil consumption during aging on Mongolian gerbil liver morphophysiology. The animals were divided into three experimental groups: the gerbils in the Adult Control Group (AC) were euthanized at 3 months of age, the gerbils in the Old Control Group (OC) at 15 months of age, and the gerbils in the Coconut Oil Group (CO) received 0.1 ml/day of coconut oil for 12 months and were euthanized at 15 months of age. Prolonged consumption of coconut oil during aging prevented the animals and the liver from gaining mass. However, the other results showed that coconut oil intensified the morphophysiological alterations of aging, promoting an increase in the hepatocyte cytoplasm and nuclei. In addition, an increase in blood vessels, reticular fibers, lipid droplets, and lipofuscin granules were observed in the CO group. Finally, the results also demonstrated that coconut oil promotes an increase in lipid peroxidation, indicated by an increase in MDA levels. We therefore conclude that coconut oil has the potential to intensify the morphophysiological alterations that occur in the liver during aging.</p>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142132994","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 : 2024-08-26DOI: 10.1016/j.jnutbio.2024.109747
Ivo Vieira de Sousa Neto, Ana Paula Pinto, Rosangela Vieira de Andrade, Fabiane Hiratsuka Veiga de Souza, Paulo Eduardo Narcizo de Souza, Victória Assis, Ramires Alsamir Tibana, Rodrigo Vanerson Passos Neves, Thiago Dos Santos Rosa, Jonato Prestes, Adelino Sanchez Ramos da Silva, Rita de Cassia Marqueti
Although previous studies demonstrated that the ancestral lifestyle can enhance the metabolic health of offspring exposed to an obesogenic diet, the specific connections between these positive effects in redox state and telomere length are unknown. We investigated the impact of paternal resistance training (RT) on stress-responsive signaling and the pathways involved in telomere homeostasis in skeletal muscle. This investigation encompassed both the fathers and first-generation litter exposed to a long-term standard diet (24 weeks) and high fat diet (HFD). Wistar rats were randomized into sedentary or trained fathers (8 weeks of resistance training). The offspring were obtained by mating with sedentary females. Upon weaning, male offspring were divided into four groups: offspring of sedentary or trained fathers exposed to either a control diet or HFD. The gastrocnemius was prepared for reverse transcription-quantitative polymerase chain reaction, immunoblotting, ELISA, and electron paramagnetic resonance spectroscopy. RT upregulated shelterin mRNA levels and antioxidant protein, preserving muscle telomere in fathers. Conversely, HFD induced a disturbance in the redox balance, which may have contributed to the offspring telomere shortening from sedentary fathers. Pre-conceptional paternal RT downregulates Kelch-like ECH-associated protein 1 (Keap1) mRNA levels in the skeletal muscle of progeny exposed to HFD, driving an increase in Glutathione reductase mRNA levels, Sod1 and Catalase protein levels to mitigate ROS production. Also, paternal exercise upregulates α-Klotho protein levels, mediating antioxidative responses without altering shelterin mRNA levels and telomere length. We provide the first in-depth analysis that the offspring's redox state seems to be directly associated with the beneficial effects of paternal exercise.
{"title":"Paternal exercise induces antioxidant defenses by α-Klotho/Keap1 pathways in the skeletal muscle of offspring exposed to a high fat-diet without changing telomere length.","authors":"Ivo Vieira de Sousa Neto, Ana Paula Pinto, Rosangela Vieira de Andrade, Fabiane Hiratsuka Veiga de Souza, Paulo Eduardo Narcizo de Souza, Victória Assis, Ramires Alsamir Tibana, Rodrigo Vanerson Passos Neves, Thiago Dos Santos Rosa, Jonato Prestes, Adelino Sanchez Ramos da Silva, Rita de Cassia Marqueti","doi":"10.1016/j.jnutbio.2024.109747","DOIUrl":"https://doi.org/10.1016/j.jnutbio.2024.109747","url":null,"abstract":"<p><p>Although previous studies demonstrated that the ancestral lifestyle can enhance the metabolic health of offspring exposed to an obesogenic diet, the specific connections between these positive effects in redox state and telomere length are unknown. We investigated the impact of paternal resistance training (RT) on stress-responsive signaling and the pathways involved in telomere homeostasis in skeletal muscle. This investigation encompassed both the fathers and first-generation litter exposed to a long-term standard diet (24 weeks) and high fat diet (HFD). Wistar rats were randomized into sedentary or trained fathers (8 weeks of resistance training). The offspring were obtained by mating with sedentary females. Upon weaning, male offspring were divided into four groups: offspring of sedentary or trained fathers exposed to either a control diet or HFD. The gastrocnemius was prepared for reverse transcription-quantitative polymerase chain reaction, immunoblotting, ELISA, and electron paramagnetic resonance spectroscopy. RT upregulated shelterin mRNA levels and antioxidant protein, preserving muscle telomere in fathers. Conversely, HFD induced a disturbance in the redox balance, which may have contributed to the offspring telomere shortening from sedentary fathers. Pre-conceptional paternal RT downregulates Kelch-like ECH-associated protein 1 (Keap1) mRNA levels in the skeletal muscle of progeny exposed to HFD, driving an increase in Glutathione reductase mRNA levels, Sod1 and Catalase protein levels to mitigate ROS production. Also, paternal exercise upregulates α-Klotho protein levels, mediating antioxidative responses without altering shelterin mRNA levels and telomere length. We provide the first in-depth analysis that the offspring's redox state seems to be directly associated with the beneficial effects of paternal exercise.</p>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142093436","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 : 2024-08-24DOI: 10.1016/j.jnutbio.2024.109748
Shichao Xiong, Qingxia Wang, Yiru Chen, Huidi Du, Yan Zhao
Background: Non-alcoholic fatty liver disease (NAFLD) begins with hepatic lipid accumulation, and leptin has anti-steatosis properties. In this study, we investigated the effects of leptin on hepatic steatosis and inflammation through the vagal pathway independently of the inhibitory effect of food intake.
Methods: Male Sprague-Dawley rats were matched for food intake after the high-fat diet (HFD)-induced obesity model and were injected intraperitoneally with leptin or leptin + lidocaine for 6 weeks. Control rats received equal volumes of saline. Adipose tissue mass, NAFLD activity scores (NAS), hepatic inflammatory factors, hepatic triglyceride content and hepatic lipid metabolism-related protein levels were evaluated.
Results: Leptin ameliorated HFD-induced hepatic lipid accumulation, improved NAS, and decreased tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and monocyte chemotactic protein-1 (MCP-1) levels in the presence of matched intake. Lidocaine decreased the phosphorylation of signal transducer and activator of transcription 3 (p-STAT3) expression in the nucleus tractus solitarius (NTS) and abrogated the leptin-mediated improvement. Leptin increased hypothalamic phosphorylated Janus kinase 2 (p-JAK2) and p-STAT3 expression, as well as the expression of mitochondrial respiratory chain-related genes. Leptin also increased hepatic phosphorylated adenosine 5'-monophosphate-activated protein kinase (p-AMPK) expression and phosphorylation of its downstream target acetyl Co A carboxylase 1 (ACC1), reducing de novo lipogenesis.
Conclusions: Our results suggest that leptin ameliorated hepatic lipid accumulation and inflammation by activating the JAK2-STAT3/AMPK pathway through the vagal pathway independently of the inhibitory effect of ingestion. Leptin has the potential to be a drug for early NAFLD treatment.
{"title":"Leptin limits hepatic lipid accumulation and inflammation via vagal activation of the JAK2-STAT3/AMPK pathway.","authors":"Shichao Xiong, Qingxia Wang, Yiru Chen, Huidi Du, Yan Zhao","doi":"10.1016/j.jnutbio.2024.109748","DOIUrl":"https://doi.org/10.1016/j.jnutbio.2024.109748","url":null,"abstract":"<p><strong>Background: </strong>Non-alcoholic fatty liver disease (NAFLD) begins with hepatic lipid accumulation, and leptin has anti-steatosis properties. In this study, we investigated the effects of leptin on hepatic steatosis and inflammation through the vagal pathway independently of the inhibitory effect of food intake.</p><p><strong>Methods: </strong>Male Sprague-Dawley rats were matched for food intake after the high-fat diet (HFD)-induced obesity model and were injected intraperitoneally with leptin or leptin + lidocaine for 6 weeks. Control rats received equal volumes of saline. Adipose tissue mass, NAFLD activity scores (NAS), hepatic inflammatory factors, hepatic triglyceride content and hepatic lipid metabolism-related protein levels were evaluated.</p><p><strong>Results: </strong>Leptin ameliorated HFD-induced hepatic lipid accumulation, improved NAS, and decreased tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and monocyte chemotactic protein-1 (MCP-1) levels in the presence of matched intake. Lidocaine decreased the phosphorylation of signal transducer and activator of transcription 3 (p-STAT3) expression in the nucleus tractus solitarius (NTS) and abrogated the leptin-mediated improvement. Leptin increased hypothalamic phosphorylated Janus kinase 2 (p-JAK2) and p-STAT3 expression, as well as the expression of mitochondrial respiratory chain-related genes. Leptin also increased hepatic phosphorylated adenosine 5'-monophosphate-activated protein kinase (p-AMPK) expression and phosphorylation of its downstream target acetyl Co A carboxylase 1 (ACC1), reducing de novo lipogenesis.</p><p><strong>Conclusions: </strong>Our results suggest that leptin ameliorated hepatic lipid accumulation and inflammation by activating the JAK2-STAT3/AMPK pathway through the vagal pathway independently of the inhibitory effect of ingestion. Leptin has the potential to be a drug for early NAFLD treatment.</p>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142073113","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 : 2024-08-22DOI: 10.1016/j.jnutbio.2024.109746
There is limited data on the effect of UV light exposure versus orally ingested vitamin D3 on vitamin D metabolism and health. A 4-week study with 16 pigs (as a model for human physiology) was conducted. The pigs were either supplemented with 20 µg/d vitamin D3 or exposed to UV light for 19 min/d to standardize plasma 25-hydroxyvitamin D3 levels. Important differences were higher levels of stored vitamin D3 in skin and subcutaneous fat, higher plasma concentrations of 3-epi-25-hydroxyvitamin D3 and increases of cutaneous lumisterol3 in UV-exposed pigs compared to supplemented pigs. UV light exposure compared to vitamin D3 supplementation resulted in lower hepatic cholesterol, higher circulating plasma nitrite, a marker of the blood pressure-lowering nitric oxide, and a reduction in the release of pro- and anti-inflammatory cytokines from stimulated peripheral blood mononuclear cells. However, plasma metabolome and stool microbiome analyses did not reveal any differences between the two groups. To conclude, the current data show important health relevant differences between oral vitamin D3 supplementation and UV light exposure. The findings may also partly explain the different vitamin D effects on health parameters obtained from association and intervention studies.
{"title":"UV light exposure versus vitamin D supplementation: A comparison of health benefits and vitamin D metabolism in a pig model","authors":"","doi":"10.1016/j.jnutbio.2024.109746","DOIUrl":"10.1016/j.jnutbio.2024.109746","url":null,"abstract":"<div><p>There is limited data on the effect of UV light exposure versus orally ingested vitamin D<sub>3</sub> on vitamin D metabolism and health. A 4-week study with 16 pigs (as a model for human physiology) was conducted. The pigs were either supplemented with 20 µg/d vitamin D<sub>3</sub> or exposed to UV light for 19 min/d to standardize plasma 25-hydroxyvitamin D<sub>3</sub> levels. Important differences were higher levels of stored vitamin D<sub>3</sub> in skin and subcutaneous fat, higher plasma concentrations of 3-epi-25-hydroxyvitamin D<sub>3</sub> and increases of cutaneous lumisterol<sub>3</sub> in UV-exposed pigs compared to supplemented pigs. UV light exposure compared to vitamin D<sub>3</sub> supplementation resulted in lower hepatic cholesterol, higher circulating plasma nitrite, a marker of the blood pressure-lowering nitric oxide, and a reduction in the release of pro- and anti-inflammatory cytokines from stimulated peripheral blood mononuclear cells. However, plasma metabolome and stool microbiome analyses did not reveal any differences between the two groups. To conclude, the current data show important health relevant differences between oral vitamin D<sub>3</sub> supplementation and UV light exposure. The findings may also partly explain the different vitamin D effects on health parameters obtained from association and intervention studies.</p></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0955286324001773/pdfft?md5=2f96b1bc89e39680af30139747a1747b&pid=1-s2.0-S0955286324001773-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142046769","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 : 2024-08-21DOI: 10.1016/j.jnutbio.2024.109738
Nonalcoholic fatty liver disease (NAFLD) has emerged as a major public health crisis with significant health threats and economic burdens worldwide in the past decades. Betaine, a naturally occurring alkaloid compound present in various dietary sources including spinach and beets, has been shown to ameliorate hepatic lipid metabolism and attenuate (NAFLD), while the underlying mechanism remains elusive. Here, we propose a novel mechanism through which betaine exerts its protective effects against hepatic lipid accumulation and (NAFLD) from an epigenetics perspective. Specifically, we discover that betaine upregulates betaine homocysteine S-methyltransferase (BHMT) expression, leading to increased nicotinamide adenine dinucleotide phosphate (NADPH) production and subsequent upregulation of fat mass and obesity-associated protein (FTO) expression. Increased abundance of FTO targets peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC1α) mRNA and reduces the N6-methyladenosine (m6A) level in the CDS of Ppargc1α transcript, which positively regulates PGC1α expression and subsequently inhibits hepatic lipid accumulation. Overall, our works demonstrate that betaine may be a promising therapeutic strategy for treating (NAFLD) and improving liver function through the regulation of (NADPH) and m6A-mediated pathways.
{"title":"Betaine alleviates nonalcoholic fatty liver disease (NAFLD) via a manner involving BHMT/FTO/m6A/ PGC1α signaling","authors":"","doi":"10.1016/j.jnutbio.2024.109738","DOIUrl":"10.1016/j.jnutbio.2024.109738","url":null,"abstract":"<div><p>Nonalcoholic fatty liver disease (NAFLD) has emerged as a major public health crisis with significant health threats and economic burdens worldwide in the past decades. Betaine, a naturally occurring alkaloid compound present in various dietary sources including spinach and beets, has been shown to ameliorate hepatic lipid metabolism and attenuate (NAFLD), while the underlying mechanism remains elusive. Here, we propose a novel mechanism through which betaine exerts its protective effects against hepatic lipid accumulation and (NAFLD) from an epigenetics perspective. Specifically, we discover that betaine upregulates betaine homocysteine S-methyltransferase (BHMT) expression, leading to increased nicotinamide adenine dinucleotide phosphate (NADPH) production and subsequent upregulation of fat mass and obesity-associated protein (FTO) expression. Increased abundance of FTO targets peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC1α) mRNA and reduces the <em>N</em><sup>6</sup>-methyladenosine (m<sup>6</sup>A) level in the CDS of <em>Ppargc1α</em> transcript, which positively regulates PGC1α expression and subsequently inhibits hepatic lipid accumulation. Overall, our works demonstrate that betaine may be a promising therapeutic strategy for treating (NAFLD) and improving liver function through the regulation of (NADPH) and m<sup>6</sup>A-mediated pathways.</p></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142000135","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 : 2024-08-16DOI: 10.1016/j.jnutbio.2024.109739
The objective of our study was to investigate the impact of neonatal overfeeding on cognitive functions and neurosteroidogenesis in male rats. Offspring were assigned to either small litters (SL; 4 pups/mother), resulting in increased milk intake and body weight gain, or normal litters (NL; 10 pups/mother). On postnatal day (PND) 21, half of the male rats were euthanized, while the remaining were kept under standard conditions (4 rats/cage) until PND70. At this stage, subjects underwent assessments for locomotor activity, anxiety levels via the elevated plus maze, and episodic-like memory (ELM) tests. By PND90, the rats were euthanized for brain dissection. Utilizing micropunch techniques, dentate gyrus (DG), CA1, and CA3 regions were extracted for analysis of mRNA expression and methylation patterns. At PND21, SL rats exhibited increased body and adipose tissue weights, alongside elevated cholesterol, glucose, and triglyceride levels compared to NL counterparts. By PND90, although metabolic disparities were no longer evident, SL rats demonstrated heightened anxiety-like behavior and diminished performance in ELM tests. Early life changes included a decreased expression of aromatase (P450arom) and 3α-HSD in CA1, with increased levels in CA3 and DG among SL rats. Additionally, PND90 rats from SL exhibited increased P450arom and decreased 5α-reductase 1 (5αR-1) expression in DG. Notably, some of these variations were correlated with changes in methylation patterns of their promoter regions. Our findings reveal that neonatal overfeeding exerts a long-term adverse effect on cognitive abilities and neurosteroidogenic pathways, underscoring the lasting impact of nutritional experiences during critical early postnatal development periods.
{"title":"Neonatal overfeeding promotes anxiety, impairs episodic-like memory, and disrupts transcriptional regulation of hippocampal steroidogenic enzymes","authors":"","doi":"10.1016/j.jnutbio.2024.109739","DOIUrl":"10.1016/j.jnutbio.2024.109739","url":null,"abstract":"<div><p>The objective of our study was to investigate the impact of neonatal overfeeding on cognitive functions and neurosteroidogenesis in male rats. Offspring were assigned to either small litters (SL; 4 pups/mother), resulting in increased milk intake and body weight gain, or normal litters (NL; 10 pups/mother). On postnatal day (PND) 21, half of the male rats were euthanized, while the remaining were kept under standard conditions (4 rats/cage) until PND70. At this stage, subjects underwent assessments for locomotor activity, anxiety levels via the elevated plus maze, and episodic-like memory (ELM) tests. By PND90, the rats were euthanized for brain dissection. Utilizing micropunch techniques, dentate gyrus (DG), CA1, and CA3 regions were extracted for analysis of mRNA expression and methylation patterns. At PND21, SL rats exhibited increased body and adipose tissue weights, alongside elevated cholesterol, glucose, and triglyceride levels compared to NL counterparts. By PND90, although metabolic disparities were no longer evident, SL rats demonstrated heightened anxiety-like behavior and diminished performance in ELM tests. Early life changes included a decreased expression of aromatase (P450arom) and 3α-HSD in CA1, with increased levels in CA3 and DG among SL rats. Additionally, PND90 rats from SL exhibited increased P450arom and decreased 5α-reductase 1 (5αR-1) expression in DG. Notably, some of these variations were correlated with changes in methylation patterns of their promoter regions. Our findings reveal that neonatal overfeeding exerts a long-term adverse effect on cognitive abilities and neurosteroidogenic pathways, underscoring the lasting impact of nutritional experiences during critical early postnatal development periods.</p></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142000172","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 : 2024-08-13DOI: 10.1016/j.jnutbio.2024.109731
The objective of this study was to investigate the influence of α-lipoic acid (LA; R enantiomer) supplementation on maternal and fetal metabolic health in pregnancies complicated by maternal obesity. Forty female Sprague-Dawley rats were randomized to one of 4 treatment groups (n=10/group) throughout prepregnancy (3 weeks) and gestation (20 days): (1) a low calorie control (CON); (2) a high calorie obesity-inducing diet (HC); (3) the HC diet with 0.25% LA (HC+LA) or; (4) the HC diet pair-fed to match the caloric intake of the HC+LA group (HC+PF). On gestation day 20, pregnant rats were placed under anesthesia for collection of maternal/fetal blood and tissues. Compared with the HC group, LA-supplemented mothers demonstrated lower maternal prepregnancy and gestational weight gain (GWG), improved glycemic control (lower homeostatic model assessment for insulin resistance), and higher cholesterol concentrations in serum [high-density lipoprotein cholesterol (HDL-C) and low-and very-low density lipoprotein cholesterol (LDL/VLDL) fractions] and liver. Male and female fetuses from LA-supplemented mothers exhibited lower body weight, improved insulin sensitivity, and evidence of altered lipid metabolism including lower serum HDL-C, lower serum triglyceride (TG), and increased hepatic TG accumulation. Although maternal LA supplementation showed some benefit for both mothers and fetuses with respect to obesity and glycemic control, concern about the potential longer-term implications of liver cholesterol (mothers) and TG accumulation (fetuses) needs further investigation.
本研究旨在探讨α-硫辛酸(LA;R对映体)补充剂对母体肥胖并发症妊娠的母体和胎儿代谢健康的影响。在整个孕前(3 周)和孕期(20 天),40 只雌性 Sprague-Dawley 大鼠被随机分为四个治疗组(n=10/组):(i) 低热量对照组(CON);(ii) 高热量诱导肥胖饮食组(HC);(iii) 含有 0.25% LA 的 HC 饮食组(HC+LA)或;(iv) 与 HC+LA 组热量摄入相匹配的 HC 饮食组(HC+PF)。在妊娠第 20 天,对孕鼠进行麻醉,以采集母体/胎儿血液和组织。与 HC 组相比,补充 LA 的母鼠妊娠前和妊娠期体重增加(GWG)较低,血糖控制有所改善(胰岛素抵抗稳态模型评估值降低),血清[高密度脂蛋白胆固醇(HDL-C)及低密度和极低密度脂蛋白胆固醇(LDL/VLDL)组分]和肝脏中的胆固醇浓度较高。补充 LA 的母亲所生的男女胎儿体重较轻,胰岛素敏感性提高,并有证据表明脂质代谢发生了改变,包括血清高密度脂蛋白胆固醇(HDL-C)降低、血清甘油三酯(TG)降低和肝脏 TG 累积增加。虽然母体补充 LA 对母亲和胎儿的肥胖和血糖控制都有一定益处,但肝脏胆固醇(母亲)和 TG 积累(胎儿)的潜在长期影响仍需进一步研究。
{"title":"Influence of maternal α-lipoic acid supplementation in Sprague Dawley rats on maternal and fetal metabolic health in pregnancies complicated by obesity","authors":"","doi":"10.1016/j.jnutbio.2024.109731","DOIUrl":"10.1016/j.jnutbio.2024.109731","url":null,"abstract":"<div><p>The objective of this study was to investigate the influence of α-lipoic acid (LA; R enantiomer) supplementation on maternal and fetal metabolic health in pregnancies complicated by maternal obesity. Forty female Sprague-Dawley rats were randomized to one of 4 treatment groups (n=10/group) throughout prepregnancy (3 weeks) and gestation (20 days): (1) a low calorie control (<strong>CON</strong>); (2) a high calorie obesity-inducing diet (<strong>HC</strong>); (3) the HC diet with 0.25% LA (<strong>HC+LA</strong>) or; (4) the HC diet pair-fed to match the caloric intake of the HC+LA group (<strong>HC+PF</strong>)<em>.</em> On gestation day 20, pregnant rats were placed under anesthesia for collection of maternal/fetal blood and tissues. Compared with the HC group, LA-supplemented mothers demonstrated lower maternal prepregnancy and gestational weight gain (GWG), improved glycemic control (lower homeostatic model assessment for insulin resistance), and higher cholesterol concentrations in serum [high-density lipoprotein cholesterol (HDL-C) and low-and very-low density lipoprotein cholesterol (LDL/VLDL) fractions] and liver. Male and female fetuses from LA-supplemented mothers exhibited lower body weight, improved insulin sensitivity, and evidence of altered lipid metabolism including lower serum HDL-C, lower serum triglyceride (TG), and increased hepatic TG accumulation. Although maternal LA supplementation showed some benefit for both mothers and fetuses with respect to obesity and glycemic control, concern about the potential longer-term implications of liver cholesterol (mothers) and TG accumulation (fetuses) needs further investigation.</p></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141988123","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 : 2024-08-13DOI: 10.1016/j.jnutbio.2024.109737
This study aimed to identify metabolic alterations in the small intestine of newborn rats with intrauterine growth restriction (IUGR), a condition linked to intestinal dysfunction. Pregnant Sprague Dawley rats underwent bilateral uterine artery ligation on gestational day 17 to induce intrauterine growth restriction or sham surgery. Rat pups were delivered spontaneously on gestational day 22. Small intestine tissues were collected on postnatal days 0 and 7 from offspring. Liquid chromatography-mass spectrometry analysis was performed to investigate untargeted metabolomic profiles. Western blot analysis assessed protein expression of key regulators. Newborn rats with intrauterine growth restriction exhibited distinct small intestine metabolic profiles compared to controls on postnatal day 0. Notably, significant alterations were observed in purine metabolism, the pentose phosphate pathway, and related pathways. Western blot analysis revealed a decrease expression in transketolase, a key enzyme of the pentose phosphate pathway, suggesting impaired activity of the pentose phosphate pathway. Additionally, decreased expression of tight junction proteins ZO-1 and occludin indicated compromised intestinal barrier function in rats with intrauterine growth restriction. Similar metabolic disruptions persisted on postnatal day 7, with further reductions in tricarboxylic acid cycle intermediates and folate biosynthesis precursors. Interestingly, lysyl-glycine, a protein synthesis marker, was elevated in rats with intrauterine growth restriction. Our findings reveal a distinct metabolic signature in the small intestine of neonatal rats with intrauterine growth restriction, characterized by disruptions in the pentose phosphate pathway, purine metabolism, and energy production pathways. These novel insights suggest potential mechanisms underlying IUGR-associated intestinal dysfunction and impaired growth.
{"title":"Altered purine and pentose phosphate pathway metabolism in uteroplacental insufficiency-induced intrauterine growth restriction offspring rats impair intestinal function","authors":"","doi":"10.1016/j.jnutbio.2024.109737","DOIUrl":"10.1016/j.jnutbio.2024.109737","url":null,"abstract":"<div><p>This study aimed to identify metabolic alterations in the small intestine of newborn rats with intrauterine growth restriction (IUGR), a condition linked to intestinal dysfunction. Pregnant Sprague Dawley rats underwent bilateral uterine artery ligation on gestational day 17 to induce intrauterine growth restriction or sham surgery. Rat pups were delivered spontaneously on gestational day 22. Small intestine tissues were collected on postnatal days 0 and 7 from offspring. Liquid chromatography-mass spectrometry analysis was performed to investigate untargeted metabolomic profiles. Western blot analysis assessed protein expression of key regulators. Newborn rats with intrauterine growth restriction exhibited distinct small intestine metabolic profiles compared to controls on postnatal day 0. Notably, significant alterations were observed in purine metabolism, the pentose phosphate pathway, and related pathways. Western blot analysis revealed a decrease expression in transketolase, a key enzyme of the pentose phosphate pathway, suggesting impaired activity of the pentose phosphate pathway. Additionally, decreased expression of tight junction proteins ZO-1 and occludin indicated compromised intestinal barrier function in rats with intrauterine growth restriction. Similar metabolic disruptions persisted on postnatal day 7, with further reductions in tricarboxylic acid cycle intermediates and folate biosynthesis precursors. Interestingly, lysyl-glycine, a protein synthesis marker, was elevated in rats with intrauterine growth restriction. Our findings reveal a distinct metabolic signature in the small intestine of neonatal rats with intrauterine growth restriction, characterized by disruptions in the pentose phosphate pathway, purine metabolism, and energy production pathways. These novel insights suggest potential mechanisms underlying IUGR-associated intestinal dysfunction and impaired growth.</p></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0955286324001682/pdfft?md5=61523c7e4d79aeff162c5d5df7a1c182&pid=1-s2.0-S0955286324001682-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141988167","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 : 2024-08-13DOI: 10.1016/j.jnutbio.2024.109716
Gestational diabetes mellitus (GDM) is prevalent among pregnant individuals and is linked to increased risks for both mothers and fetuses. Although GDM is known to cause disruptions in gut microbiota and metabolites, their potential transmission to the fetus has not been fully explored. This study aimed to characterize the similarities in microbial and metabolic signatures between mothers with GDM and their neonates as well as the interactions between these signatures. This study included 89 maternal-neonate pairs (44 in the GDM group and 45 in the normoglycemic group). We utilized 16S rRNA gene sequencing and untargeted metabolomics to analyze the gut microbiota and plasma metabolomics of mothers and neonates. Integrative analyses were performed to elucidate the interactions between these omics. Distinct microbial and metabolic signatures were observed in GDM mothers and their neonates compared to those in the normoglycemic group. Fourteen genera showed similar alterations across both groups. Metabolites linked to glucose, lipid, and energy metabolism were differentially influenced in GDM, with similar trends observed in both mothers and neonates in the GDM group. Network analysis indicated significant associations between Qipengyuania and metabolites related to bile acid metabolism in mothers and newborns. Furthermore, we observed a significant correlation between several genera and metabolites and clinical phenotypes in normoglycemic mothers and newborns, but these correlations were disrupted in the GDM group. Our findings suggest that GDM consistently affects both the microbiota and metabolome in mothers and neonates, thus elucidating the mechanism underlying metabolic transmission across generations. These insights contribute to knowledge regarding the multiomics interactions in GDM and underscore the need to further investigate the prenatal environmental impacts on offspring metabolism.
{"title":"Landscapes of maternal and neonatal gut microbiome and plasma metabolome signatures and their interaction in gestational diabetes mellitus","authors":"","doi":"10.1016/j.jnutbio.2024.109716","DOIUrl":"10.1016/j.jnutbio.2024.109716","url":null,"abstract":"<div><p>Gestational diabetes mellitus (GDM) is prevalent among pregnant individuals and is linked to increased risks for both mothers and fetuses. Although GDM is known to cause disruptions in gut microbiota and metabolites, their potential transmission to the fetus has not been fully explored. This study aimed to characterize the similarities in microbial and metabolic signatures between mothers with GDM and their neonates as well as the interactions between these signatures. This study included 89 maternal-neonate pairs (44 in the GDM group and 45 in the normoglycemic group). We utilized 16S rRNA gene sequencing and untargeted metabolomics to analyze the gut microbiota and plasma metabolomics of mothers and neonates. Integrative analyses were performed to elucidate the interactions between these omics. Distinct microbial and metabolic signatures were observed in GDM mothers and their neonates compared to those in the normoglycemic group. Fourteen genera showed similar alterations across both groups. Metabolites linked to glucose, lipid, and energy metabolism were differentially influenced in GDM, with similar trends observed in both mothers and neonates in the GDM group. Network analysis indicated significant associations between <em>Qipengyuania</em> and metabolites related to bile acid metabolism in mothers and newborns. Furthermore, we observed a significant correlation between several genera and metabolites and clinical phenotypes in normoglycemic mothers and newborns, but these correlations were disrupted in the GDM group. Our findings suggest that GDM consistently affects both the microbiota and metabolome in mothers and neonates, thus elucidating the mechanism underlying metabolic transmission across generations. These insights contribute to knowledge regarding the multiomics interactions in GDM and underscore the need to further investigate the prenatal environmental impacts on offspring metabolism.</p></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141988124","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}