Julia Kühn , Corinna Brandsch , Anja C. Bailer , Mikis Kiourtzidis , Frank Hirche , Chia-Yu Chen , Lajos Markó , Theda U.P. Bartolomaeus , Ulrike Löber , Samira Michel , Monika Wensch-Dorendorf , Sofia K. Forslund-Startceva , Gabriele I. Stangl
{"title":"UV light exposure versus vitamin D supplementation: A comparison of health benefits and vitamin D metabolism in a pig model","authors":"Julia Kühn , Corinna Brandsch , Anja C. Bailer , Mikis Kiourtzidis , Frank Hirche , Chia-Yu Chen , Lajos Markó , Theda U.P. Bartolomaeus , Ulrike Löber , Samira Michel , Monika Wensch-Dorendorf , Sofia K. Forslund-Startceva , Gabriele I. Stangl","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":"134 ","pages":"Article 109746"},"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}
Jiaqi Liu , Yuxi Liu , Yushi Chen , Youhua Liu , Chaoqun Huang , Yaojun Luo , Xinxia Wang
{"title":"Betaine alleviates nonalcoholic fatty liver disease (NAFLD) via a manner involving BHMT/FTO/m6A/ PGC1α signaling","authors":"Jiaqi Liu , Yuxi Liu , Yushi Chen , Youhua Liu , Chaoqun Huang , Yaojun Luo , Xinxia Wang","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":"134 ","pages":"Article 109738"},"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}
{"title":"Neonatal overfeeding promotes anxiety, impairs episodic-like memory, and disrupts transcriptional regulation of hippocampal steroidogenic enzymes","authors":"Maria Florencia Rossetti , Rocio Schumacher , Guillermina Canesini , Pamela Fernandez , Luisa Gaydou , Cora Stoker , Jorge Guillermo Ramos","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":"134 ","pages":"Article 109739"},"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}
Gabriella A. Andreani , Saleh Mahmood , Kok Lim Kua , Mulchand S. Patel , Todd C. Rideout
{"title":"Influence of maternal α-lipoic acid supplementation in Sprague Dawley rats on maternal and fetal metabolic health in pregnancies complicated by obesity","authors":"Gabriella A. Andreani , Saleh Mahmood , Kok Lim Kua , Mulchand S. Patel , Todd C. Rideout","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":"134 ","pages":"Article 109731"},"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}
{"title":"Altered purine and pentose phosphate pathway metabolism in uteroplacental insufficiency-induced intrauterine growth restriction offspring rats impair intestinal function","authors":"Sheng-Yuan Ho , Merryl Esther Yuliana , Hsiu-Chu Chou , Liang-Ti Huang , Chung-Ming Chen","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":"134 ","pages":"Article 109737"},"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}
Jieying Liu , Xiao Zhai , Lu Ding , Miao Yu , Qian Zhang , Juntao Liu , Yingna Song , Liangkun Ma , Xinhua Xiao
{"title":"Landscapes of maternal and neonatal gut microbiome and plasma metabolome signatures and their interaction in gestational diabetes mellitus","authors":"Jieying Liu , Xiao Zhai , Lu Ding , Miao Yu , Qian Zhang , Juntao Liu , Yingna Song , Liangkun Ma , Xinhua Xiao","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":"134 ","pages":"Article 109716"},"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}
Aurélien Brun , Philippe Denis , Mathieu Rambeau , Jean-Paul Rigaudière , Chrystèle Jouve , Vera Mazurak , Frédéric Capel
{"title":"Polyunsaturated fatty acids prevent myosteatosis and lipotoxicity","authors":"Aurélien Brun , Philippe Denis , Mathieu Rambeau , Jean-Paul Rigaudière , Chrystèle Jouve , Vera Mazurak , Frédéric Capel","doi":"10.1016/j.jnutbio.2024.109722","DOIUrl":"10.1016/j.jnutbio.2024.109722","url":null,"abstract":"<div><p>Myosteatosis occurs in response to excess circulating fatty acids and is associated with muscle dysfunction. This study aimed to characterize the sequence of events of lipid-induced toxicity within muscle cells and the role of polyunsaturated fatty acids (PUFA) as potential preventive factors. Myosteatosis was induced in C2C12 myotubes exposed to palmitic acid (PAL 500µM). Furthermore, cells were co-incubated with PUFA (α-linolenic acid = ALA, Eicosapentaenoic acid = EPA, Docosahexaenoic acid = DHA; Arachidonic acid = ARA) over a period of 48 h. Cell viability, morphology, and measures of lipid and protein metabolism were assessed at 6, 12, 24, and 48 h. We observed that myotube integrity was rapidly and progressively disrupted by PAL treatment after 12 h, ultimately leading to cell death (41.7% cell survival at 48 h, <em>p</em> < .05). Cell death did not occur in cells exposed to PAL+ARA and PAL+DHA. After 6 h of PAL treatment, an accumulation of large lipid droplets was observed within the cell (6 folds, <em>p</em> < .05). This was associated with an increase in ceramides (CER x3 fold change) and diacylglycerol (DAG x150 fold change) contents (<em>p</em> < .05). At the same time, insulin was no longer able to stimulate protein synthesis (<em>p</em> < .05) nor leverage autophagic flux (<em>p</em> < .05). DHA and ARA were able to completely reverse the defect in protein synthesis and partially modulate the accumulation of CER and DAG. These findings present new and intriguing research avenues in the field of muscle metabolism and nutrition, particularly in the context of aging, chronic muscle disorders, and insulin resistance.</p></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"134 ","pages":"Article 109722"},"PeriodicalIF":4.8,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141982569","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}
Kajs Hadžić , András Gregor , Barbara Kofler , Marc Pignitter , Kalina Duszka
{"title":"The beneficial impact of ketogenic diets on chemically-induced colitis in mice depends on the diet's lipid composition","authors":"Kajs Hadžić , András Gregor , Barbara Kofler , Marc Pignitter , Kalina Duszka","doi":"10.1016/j.jnutbio.2024.109736","DOIUrl":"10.1016/j.jnutbio.2024.109736","url":null,"abstract":"<div><p>Previously, we showed that restrictive diets, including ketogenic diet (KD), have an anti-inflammatory impact on the healthy gastrointestinal tract of mice. Afterward, we found that energy-restricting diets mitigate inflammation in the dextran sodium sulfate (DSS) colitis mouse model. The current study aimed to verify the impact of KD on DSS colitis and assess if the diet's fat composition influences the outcomes of the intervention.</p><p>Mice with mild chronic colitis were fed control chow, KD composed of long-chain triglycerides (KD LCT) or a KD containing a mix of LCT and medium-chain triglycerides (KD LCT/MCT).</p><p>KDs did not reverse DSS-enhanced gut permeability and shortening of the colon. Both KDs had a similar impact on liver, cecum, and spleen weight, villi and colon length, the thickness of muscularis externa, and expression of ZO-1 and occludin. On the contrary, body weight, glutathione (GSH) and taurine-GSH levels, GSH-S transferase (GST), and myeloperoxidase (MPO) activity, as well as an abundance of several fecal bacteria, all were differentially affected by the two types of KDs. When compared to the DSS control diet, reduction in colon mucosa cytokines expression was stronger in KD LCT than in the KD LCT/MCT group.</p><p>We conclude that the outcomes of the KD interventions in terms of potential therapeutical applications depend on lipid composition. KD LCT showed a strong positive impact on gut inflammation. A potential contribution of GSH to KD outcomes and a correlation between MPO activity and microbiota composition was identified.</p></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"134 ","pages":"Article 109736"},"PeriodicalIF":4.8,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0955286324001670/pdfft?md5=d7cba16ba28c25ee5ccaa1f33c1239ae&pid=1-s2.0-S0955286324001670-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141916957","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}
André Tiago Malveira , Victor Hugo Dantas Guimarães , Sonielle Rodrigues Lima , Lucyana Conceição Farias , Alfredo Maurício Batista de Paula , André Luiz Sena Guimarães , Sérgio Henrique Sousa Santos
{"title":"Development of a malnutrition model in mice: Comparative evaluation of food restriction percentage and different diets","authors":"André Tiago Malveira , Victor Hugo Dantas Guimarães , Sonielle Rodrigues Lima , Lucyana Conceição Farias , Alfredo Maurício Batista de Paula , André Luiz Sena Guimarães , Sérgio Henrique Sousa Santos","doi":"10.1016/j.jnutbio.2024.109721","DOIUrl":"10.1016/j.jnutbio.2024.109721","url":null,"abstract":"<div><p>Malnutrition is a complicated illness that affects people worldwide and is linked to higher death rates, a heightened vulnerability to infections, and delayed cognitive development. Experimental models have been constructed to comprehend the mechanisms associated with hunger. In this regard, the current study used two different types of food aiming to validate a murine model of malnutrition based on dietary restriction. The study was conducted with fifty-six Swiss male mice (eight-week-old) divided into eight groups (n=7 each) and fed the following experimental diets (10 weeks): Standard Diet (ST) ad libitum; ST 20% dietary restriction; ST 40% dietary restriction; ST 60% dietary restriction; AIN93-M diet ad libitum; AIN93-M 20% dietary restriction; AIN93-M 40% dietary restriction; AIN93-M 60% dietary restriction. Body, biochemical, and histological parameters were measured, and the restriction effects on genes related to oxidative stress (GPX1 and GPX4) in epididymal adipose tissue were evaluated. The results obtained showed that 20%, 40%, and 60% of dietary restrictions were able to reduce body weight when compared to controls, highlighting the accentuated weight loss in animals with 60% restrictions, especially those fed with AIN-93 M, which showed physical changes such as whitish skin and dull coat, voracious eating, and hunched posture. The present animal model also showed biochemical changes with hypoalbuminemia, as well as histological epididymal adipose tissue modulation. The presence of increased oxidative stress was observed when evaluating the GPX4 gene. Given the results, 60% food restriction using the AIN93-M diet was the best protocol for inducing malnutrition.</p></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"134 ","pages":"Article 109721"},"PeriodicalIF":4.8,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141916956","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}
Ying Wu , Yiting Gong , Yiming Ma , Qiaofan Zhao , Ruyu Fu , Xiaoming Zhang , Ye Li , Xueyuan Zhi
{"title":"Effects of vitamin D status on cutaneous wound healing through modulation of EMT and ECM","authors":"Ying Wu , Yiting Gong , Yiming Ma , Qiaofan Zhao , Ruyu Fu , Xiaoming Zhang , Ye Li , Xueyuan Zhi","doi":"10.1016/j.jnutbio.2024.109733","DOIUrl":"10.1016/j.jnutbio.2024.109733","url":null,"abstract":"<div><p>To investigate the effects of vitamin D status on cutaneous wound healing, C57BL/6J mice were fed diets with different vitamin D levels or injected intraperitoneally with 1α,25(OH)<sub>2</sub>D<sub>3</sub>. Dorsal skin wounds were created and wound edge tissues were collected on days 4, 7, 11, and 14 postwounding. The proliferation and migration of HaCaT cells treated with shVDR or 1α,25(OH)<sub>2</sub>D<sub>3</sub> were assessed. Vitamin D deficiency (VDD) decreased wound closure and might delay inflammatory response, shown by slower inflammatory cell infiltration, decreased IL6 and TNF expression in early phase followed by an increase later. VDD might postpone epithelial-mesenchymal transition (EMT), initially characterized by higher epithelial markers and lower mesenchymal markers, followed by opposite appearance later. Dietary vitamin D supplementation and 1α,25(OH)<sub>2</sub>D<sub>3</sub> intervention tended to accelerate EMT. Regarding extracellular matrix (ECM), VDD appeared to reduce collagen deposition on day 4 and downregulated fibronectin, COL3A1, and MMP9 expression early, followed by an increase later, together with an initial increase and subsequent decrease in <em>Timp1</em> mRNA expression. Dietary vitamin D intervention promoted fibronectin and MMP9 expression on day 4 and then downregulated their expression on day 14. TGFb1/SMAD2/3 signaling seemed to be downregulated by VDD and upregulated by 1α,25(OH)<sub>2</sub>D<sub>3</sub>. In vitro, partial inhibition of VDR by shVDR tended to inhibit HaCaT cell proliferation and migration, EMT, and TGFb1/SMAD2/3 signaling, whereas 1α,25(OH)<sub>2</sub>D<sub>3</sub> appeared to generate opposite effects. In conclusion, VDD hindered cutaneous wound healing, potentially due to impaired inflammatory response, delayed EMT, decreased ECM, and inhibited TGFb1/SMAD2/3 pathway. Vitamin D and 1α,25(OH)<sub>2</sub>D<sub>3</sub> tended to enhance EMT and ECM.</p></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"134 ","pages":"Article 109733"},"PeriodicalIF":4.8,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141913031","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}