Pub Date : 2025-03-20DOI: 10.1016/j.metop.2025.100359
Jingyi Ni , Baicheng Wang , Xinyue Liu , Rui Yin , Jinlin Tang , Siyu Hua , Xiaoxiao Zhang , Yangyang Wu , Shihu Zhang , Chenbo Ji
Celastrol is widely recognized as one of the most potent anti-obesity agents, and its ability to promote adipocyte thermogenesis is thought to be a key mechanism. However, the precise molecular targets through which celastrol modulates thermogenesis in human adipocytes remain unclear. In this study, we synthesized a celastrol-based small molecular probe and employed a combination of photoaffinity labeling (PAL), click chemistry, and Surface Plasmon Resonance (SPR) to identify its direct binding targets. Our results reveal that celastrol directly interacts with creatine kinase B-type (CKB), leading to an increase in CKB protein stability. This suggests that celastrol modulates the futile creatine cycle within human brown adipocytes, thereby contributing to thermogenesis. Collectively, our findings provide new insights into the molecular mechanisms by which celastrol promotes thermogenesis in human brown adipocytes. Notably, we demonstrated that celastrol targets CKB-mediated futile creatine cycle for the first time. These findings not only deepen our understanding of celastrol's role in weight loss but also provides a potential strategy for obesity treatment.
{"title":"Celastrol targets CKB-mediated futile creatine cycle in human brown adipocytes thermogenesis","authors":"Jingyi Ni , Baicheng Wang , Xinyue Liu , Rui Yin , Jinlin Tang , Siyu Hua , Xiaoxiao Zhang , Yangyang Wu , Shihu Zhang , Chenbo Ji","doi":"10.1016/j.metop.2025.100359","DOIUrl":"10.1016/j.metop.2025.100359","url":null,"abstract":"<div><div>Celastrol is widely recognized as one of the most potent anti-obesity agents, and its ability to promote adipocyte thermogenesis is thought to be a key mechanism. However, the precise molecular targets through which celastrol modulates thermogenesis in human adipocytes remain unclear. In this study, we synthesized a celastrol-based small molecular probe and employed a combination of photoaffinity labeling (PAL), click chemistry, and Surface Plasmon Resonance (SPR) to identify its direct binding targets. Our results reveal that celastrol directly interacts with creatine kinase B-type (CKB), leading to an increase in CKB protein stability. This suggests that celastrol modulates the futile creatine cycle within human brown adipocytes, thereby contributing to thermogenesis. Collectively, our findings provide new insights into the molecular mechanisms by which celastrol promotes thermogenesis in human brown adipocytes. Notably, we demonstrated that celastrol targets CKB-mediated futile creatine cycle for the first time. These findings not only deepen our understanding of celastrol's role in weight loss but also provides a potential strategy for obesity treatment.</div></div>","PeriodicalId":94141,"journal":{"name":"Metabolism open","volume":"26 ","pages":"Article 100359"},"PeriodicalIF":0.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143685345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-11DOI: 10.1016/j.metop.2025.100357
Nancy Safwan , Christos S. Mantzoros , Maya Rahme , Rafic Baddoura , Georges Halaby , Ghada El-Hajj Fuleihan
Aims
To compare the performance of newer insulin resistance (IR) indices, triglyceride glucose index (TyG) and metabolic score for IR (METS-IR), with previous markers HOMA-IR and McAuley-IR, and assess the impact of one-year of vitamin D supplementation, at two doses, on these indices in overweight, elderly individuals.
Methods
Exploratory analyses from a double-blind, multicenter randomized controlled trial involved overweight elderly participants with baseline serum 25-hydroxyvitamin D [25(OH)D] levels of 10–30 ng/ml (clinicaltrial.gov: NCT01315366). Participants received 1000 mg calcium citrate/day and vitamin D supplementation at a low-dose of 600 IU/day, or high-dose of 3750 IU/day.
Results
221 participants received low or high-dose vitamin D supplementation. Mean age was 71 ± 5 years, BMI 30 ± 4 kg/m2, 25(OH)D 20 ± 7 ng/ml, with 55 % female and 69 % with prediabetes. There were no significant baseline differences except for HDL levels (p = 0.04). TyG was notably increased in the high-dose group (p = 0.02). Mixed linear model analysis showed a greater increase in serum 25(OH)D in the high-dose group compared to the low-dose, with decreases in PTH, cholesterol, and LDL independent of dose. TyG and METS-IR did not differ by dose, time, or dose∗time interaction. Subgroup analyses by sex, baseline 25(OH)D cut-off, and glucose tolerance status were null. FokI polymorphism showed a significantly greater METS-IR in the high-dose arm, disappeared after adjusting for fat mass. McAuley-IR was the best IR index compared to TyG and METS-IR, both at baseline and 12 months.
Conclusions
Vitamin D supplementation at 3750 IU/d over one-year did not improve IR markers, including TyG and METS-IR.
{"title":"Vitamin D supplementation at low (600 IU/day) or higher dose (3,750 IU/day) does not improve insulin resistance markers at one year: A randomized controlled trial","authors":"Nancy Safwan , Christos S. Mantzoros , Maya Rahme , Rafic Baddoura , Georges Halaby , Ghada El-Hajj Fuleihan","doi":"10.1016/j.metop.2025.100357","DOIUrl":"10.1016/j.metop.2025.100357","url":null,"abstract":"<div><h3>Aims</h3><div>To compare the performance of newer insulin resistance (IR) indices, triglyceride glucose index (TyG) and metabolic score for IR (METS-IR), with previous markers HOMA-IR and McAuley-IR, and assess the impact of one-year of vitamin D supplementation, at two doses, on these indices in overweight, elderly individuals.</div></div><div><h3>Methods</h3><div>Exploratory analyses from a double-blind, multicenter randomized controlled trial involved overweight elderly participants with baseline serum 25-hydroxyvitamin D [25(OH)D] levels of 10–30 ng/ml (clinicaltrial.gov: NCT01315366). Participants received 1000 mg calcium citrate/day and vitamin D supplementation at a low-dose of 600 IU/day, or high-dose of 3750 IU/day.</div></div><div><h3>Results</h3><div>221 participants received low or high-dose vitamin D supplementation. Mean age was 71 ± 5 years, BMI 30 ± 4 kg/m<sup>2</sup>, 25(OH)D 20 ± 7 ng/ml, with 55 % female and 69 % with prediabetes. There were no significant baseline differences except for HDL levels (p = 0.04). TyG was notably increased in the high-dose group (p = 0.02). Mixed linear model analysis showed a greater increase in serum 25(OH)D in the high-dose group compared to the low-dose, with decreases in PTH, cholesterol, and LDL independent of dose. TyG and METS-IR did not differ by dose, time, or dose∗time interaction. Subgroup analyses by sex, baseline 25(OH)D cut-off, and glucose tolerance status were null. <em>Fok</em>I polymorphism showed a significantly greater METS-IR in the high-dose arm, disappeared after adjusting for fat mass. McAuley-IR was the best IR index compared to TyG and METS-IR, both at baseline and 12 months.</div></div><div><h3>Conclusions</h3><div>Vitamin D supplementation at 3750 IU/d over one-year did not improve IR markers, including TyG and METS-IR.</div></div>","PeriodicalId":94141,"journal":{"name":"Metabolism open","volume":"26 ","pages":"Article 100357"},"PeriodicalIF":0.0,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143685201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-05DOI: 10.1016/j.metop.2025.100355
Mehreen Khan , Lusine Gigoyan , Mary Reed
Aims
Remote monitoring can support patients with Type II diabetes. Still, evidence for improved glucose outcomes in broad community practice patients is extremely limited. We examined remote glucose monitoring in newly diagnosed patients with diabetes to identify its impact on diabetes outcomes.
Methods
In a retrospective cohort study of all adults (age 18–75) with newly diagnosed Type II diabetes February 2020–December 2021 in a large integrated health system, we compared HbA1c (units: percentage, %) outcomes in remote monitoring users to non-users in their first year with diabetes, using propensity-weighted analyses.
Results
Among 35,958 patients, patients age 45+ (vs. age 18–34), who were Asian/Pacific Islander or Hispanic (compared to White), living in more deprived neighborhoods, not using the patient portal, or with baseline HbA1c ≤ 8 were significantly (p < 0.001) less likely to use remote glucose monitoring. After adjustment, remote monitoring use was associated with a 23 % (95 % CI: 17–29 %) higher rate of reaching the HbA1c ≤ 8 % (vs. non-users). In patients starting with HbA1c > 8, remote glucose monitoring use was associated with 0.93 % greater absolute improvement in HbA1c value (vs. non-users, p < 0.05).
Conclusions
Remote glucose monitoring was associated with improved HbA1c among newly diagnosed patients with Type II diabetes.
{"title":"Remote glucose monitoring and HbA1c improvement among persons with newly diagnosed diabetes mellitus type 2: A multi-center community-based study","authors":"Mehreen Khan , Lusine Gigoyan , Mary Reed","doi":"10.1016/j.metop.2025.100355","DOIUrl":"10.1016/j.metop.2025.100355","url":null,"abstract":"<div><h3>Aims</h3><div>Remote monitoring can support patients with Type II diabetes. Still, evidence for improved glucose outcomes in broad community practice patients is extremely limited. We examined remote glucose monitoring in newly diagnosed patients with diabetes to identify its impact on diabetes outcomes.</div></div><div><h3>Methods</h3><div>In a retrospective cohort study of all adults (age 18–75) with newly diagnosed Type II diabetes February 2020–December 2021 in a large integrated health system, we compared HbA1c (units: percentage, %) outcomes in remote monitoring users to non-users in their first year with diabetes, using propensity-weighted analyses.</div></div><div><h3>Results</h3><div>Among 35,958 patients, patients age 45+ (vs. age 18–34), who were Asian/Pacific Islander or Hispanic (compared to White), living in more deprived neighborhoods, not using the patient portal, or with baseline HbA1c ≤ 8 were significantly (p < 0.001) less likely to use remote glucose monitoring. After adjustment, remote monitoring use was associated with a 23 % (95 % CI: 17–29 %) higher rate of reaching the HbA1c ≤ 8 % (vs. non-users). In patients starting with HbA1c > 8, remote glucose monitoring use was associated with 0.93 % greater absolute improvement in HbA1c value (vs. non-users, p < 0.05).</div></div><div><h3>Conclusions</h3><div>Remote glucose monitoring was associated with improved HbA1c among newly diagnosed patients with Type II diabetes.</div></div>","PeriodicalId":94141,"journal":{"name":"Metabolism open","volume":"26 ","pages":"Article 100355"},"PeriodicalIF":0.0,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143610823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-01DOI: 10.1016/j.metop.2024.100340
Chengbin Li, Junli Liu, Bin Liang
{"title":"SPT: A new contributor to trans fatty acid-induced atherosclerosis","authors":"Chengbin Li, Junli Liu, Bin Liang","doi":"10.1016/j.metop.2024.100340","DOIUrl":"10.1016/j.metop.2024.100340","url":null,"abstract":"","PeriodicalId":94141,"journal":{"name":"Metabolism open","volume":"25 ","pages":"Article 100340"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143611695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-01DOI: 10.1016/j.metop.2024.100335
Yifan Zhou, Junli Liu
{"title":"The role of lipoprotein sulfatides in MASLD fibrosis transition: A new frontier in hepatic immunomodulation","authors":"Yifan Zhou, Junli Liu","doi":"10.1016/j.metop.2024.100335","DOIUrl":"10.1016/j.metop.2024.100335","url":null,"abstract":"","PeriodicalId":94141,"journal":{"name":"Metabolism open","volume":"25 ","pages":"Article 100335"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143611694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-01DOI: 10.1016/j.metop.2025.100354
Xiaozhen Guo , Zixuan Zhang , Cuina Li , Xueling Li , Yutang Cao , Yangyang Wang , Jiaqi Li , Yibin Wang , Kanglong Wang , Yameng Liu , Cen Xie , Yifei Zhong
Background
Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease, affecting over 30 % of diabetes mellitus (DM) patients. Early detection of DKD in DM patients can enable timely preventive therapies, and potentially delay disease progression. Since the kidney relies on fatty acid oxidation for energy, dysregulated lipid metabolism has been implicated in proximal tubular cell damage and DKD pathogenesis. This study aimed to identify lipid alterations during DKD development and potential biomarkers differentiating DKD from DM.
Methods
lipidomics analysis was performed on serum collected from 55 patients with DM, 21 with early DKD stage and 32 with advanced DKD, and 22 healthy subjects. Associations between lipids and DKD risk were evaluated by logistic regression.
Results
Lipid profiling revealed elevated levels of certain lysophosphatidylethanolamines (LPEs), phosphatidylethanolamines (PEs), ceramides (Cers), and diacylglycerols (DAGs) in the DM-DKD transition, while most LPEs, lysophosphatidylcholines (LPCs), along with several monoacylglycerol (MAG) and triacylglycerols (TAGs), increased further from DKD-E to DKD-A. Logistic regression indicated positive associations between LPCs, LPEs, PEs, and DAGs with DKD risk, with most LPEs correlating significantly with urinary albumin-to-creatinine ratio (UACR) and inversely with estimated glomerular filtration rate (eGFR). A machine-learning-derived biomarker panel, Lipid9, consisting of LPC(18:2), LPC(20:5), LPE (16:0), LPE (18:0), LPE (18:1), LPE (24:0), PE (34:1), PE (34:2), and PE (36:2), accurately distinguished DKD (AUC: 0.78, 95 % CI 0.68–0.86) from DM. Incorporating two clinical indexes, serum creatinine and blood urea nitrogen, the Lipid9-SCB model further improved DKD detection (AUC: 0.83, 95 % CI 0.75–0.90) from DM, and was notably more sensitive for identifying DKD-E (AUC: 0.79, 95 % CI 0.67–0.91).
Conclusion
This study deciphers the lipid signature in DKD progression, and suggests the Lipid9-SCB panel as a promising tool for early DKD detection in DM patients.
背景：糖尿病肾病（DKD）是终末期肾脏疾病的主要原因，影响了超过30%的糖尿病（DM）患者。早期发现糖尿病患者的DKD可以及时预防治疗，并有可能延缓疾病进展。由于肾脏依赖脂肪酸氧化提供能量，脂质代谢失调与近端小管细胞损伤和DKD发病机制有关。本研究旨在确定DKD发展过程中的脂质改变以及区分DKD和DM的潜在生物标志物。方法对55名DM患者、21名早期DKD患者和32名晚期DKD患者以及22名健康受试者的血清进行滑质组学分析。通过逻辑回归评估脂质与DKD风险之间的关系。结果在DM-DKD转化过程中，某些溶血磷脂酰乙醇胺（LPEs）、磷脂酰乙醇胺（PEs）、神经酰胺（Cers）和二酰基甘油（dag）水平升高，而大多数LPEs、溶血磷脂酰胆碱（LPCs）以及一些单酰基甘油（MAG）和三酰基甘油（TAGs）在DKD-E到DKD-A之间进一步升高。Logistic回归显示LPCs、LPEs、PEs和dag与DKD风险呈正相关，大多数LPEs与尿白蛋白与肌酐比（UACR）显著相关，与肾小球滤过率（eGFR）估算呈负相关。由LPC（18:2）、LPC（20:5）、LPE（16:0）、LPE（18:0）、LPE（18:1）、LPE（24:0）、PE（34:1）、PE（34:2）和PE（36:2）组成的机器学习衍生的生物标志物面板Lipid9准确区分了DKD和DM （AUC: 0.78, 95% CI 0.68-0.86）。结合血清肌酐和血尿素氮两项临床指标，Lipid9- scb模型进一步提高了DKD和DM的检测（AUC: 0.83, 95% CI 0.75-0.90），对DKD- e的识别（AUC: 0.79, 95% CI 0.67-0.91）更为敏感。结论：本研究揭示了DKD进展中的脂质特征，并提示Lipid9-SCB面板是DM患者早期DKD检测的有希望的工具。
{"title":"Lipidomics reveals potential biomarkers and pathophysiological insights in the progression of diabetic kidney disease","authors":"Xiaozhen Guo , Zixuan Zhang , Cuina Li , Xueling Li , Yutang Cao , Yangyang Wang , Jiaqi Li , Yibin Wang , Kanglong Wang , Yameng Liu , Cen Xie , Yifei Zhong","doi":"10.1016/j.metop.2025.100354","DOIUrl":"10.1016/j.metop.2025.100354","url":null,"abstract":"<div><h3>Background</h3><div>Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease, affecting over 30 % of diabetes mellitus (DM) patients. Early detection of DKD in DM patients can enable timely preventive therapies, and potentially delay disease progression. Since the kidney relies on fatty acid oxidation for energy, dysregulated lipid metabolism has been implicated in proximal tubular cell damage and DKD pathogenesis. This study aimed to identify lipid alterations during DKD development and potential biomarkers differentiating DKD from DM.</div></div><div><h3>Methods</h3><div>lipidomics analysis was performed on serum collected from 55 patients with DM, 21 with early DKD stage and 32 with advanced DKD, and 22 healthy subjects. Associations between lipids and DKD risk were evaluated by logistic regression.</div></div><div><h3>Results</h3><div>Lipid profiling revealed elevated levels of certain lysophosphatidylethanolamines (LPEs), phosphatidylethanolamines (PEs), ceramides (Cers), and diacylglycerols (DAGs) in the DM-DKD transition, while most LPEs, lysophosphatidylcholines (LPCs), along with several monoacylglycerol (MAG) and triacylglycerols (TAGs), increased further from DKD-E to DKD-A. Logistic regression indicated positive associations between LPCs, LPEs, PEs, and DAGs with DKD risk, with most LPEs correlating significantly with urinary albumin-to-creatinine ratio (UACR) and inversely with estimated glomerular filtration rate (eGFR). A machine-learning-derived biomarker panel, Lipid9, consisting of LPC(18:2), LPC(20:5), LPE (16:0), LPE (18:0), LPE (18:1), LPE (24:0), PE (34:1), PE (34:2), and PE (36:2), accurately distinguished DKD (AUC: 0.78, 95 % CI 0.68–0.86) from DM. Incorporating two clinical indexes, serum creatinine and blood urea nitrogen, the Lipid9-SCB model further improved DKD detection (AUC: 0.83, 95 % CI 0.75–0.90) from DM, and was notably more sensitive for identifying DKD-E (AUC: 0.79, 95 % CI 0.67–0.91).</div></div><div><h3>Conclusion</h3><div>This study deciphers the lipid signature in DKD progression, and suggests the Lipid9-SCB panel as a promising tool for early DKD detection in DM patients.</div></div>","PeriodicalId":94141,"journal":{"name":"Metabolism open","volume":"25 ","pages":"Article 100354"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143561891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-08DOI: 10.1016/j.metop.2025.100353
Maria Chouli , Anastasia Bothou , Giannoula Kyrkou , Sofia Kaliarnta , Aikaterini Dimitrakopoulou , Athina Diamanti
This review examines nutritional needs during pregnancy and lactation, focusing on the critical nutrients required for both maternal and fetal health. Essential nutrients such as folic acid, vitamin D, iron, calcium, and omega-3 fatty acids play a significant role in supporting fetal development and minimizing the risk of complications like gestational diabetes, hypertension, and preterm birth. Various dietary patterns, including the Mediterranean, vegetarian/vegan, and gluten-free diets, were evaluated for their adequacy and potential benefits. The Mediterranean diet was highlighted for its protective effects against pregnancy-related health issues. In contrast, the review identified vegetarian and vegan diets as requiring careful planning to ensure sufficient intake of key nutrients. Additionally, the review explored the implications of gestational diabetes and dietary strategies for managing blood sugar levels. The effects of intermittent fasting during pregnancy were also discussed, with mixed evidence regarding its safety and impact on pregnancy outcomes. Overall, the review stresses the importance of tailored nutritional guidance to ensure optimal health for both the mother and the developing fetus during pregnancy and lactation.
{"title":"An updated review of popular dietary patterns during pregnancy and lactation: Trends, benefits, and challenges","authors":"Maria Chouli , Anastasia Bothou , Giannoula Kyrkou , Sofia Kaliarnta , Aikaterini Dimitrakopoulou , Athina Diamanti","doi":"10.1016/j.metop.2025.100353","DOIUrl":"10.1016/j.metop.2025.100353","url":null,"abstract":"<div><div>This review examines nutritional needs during pregnancy and lactation, focusing on the critical nutrients required for both maternal and fetal health. Essential nutrients such as folic acid, vitamin D, iron, calcium, and omega-3 fatty acids play a significant role in supporting fetal development and minimizing the risk of complications like gestational diabetes, hypertension, and preterm birth. Various dietary patterns, including the Mediterranean, vegetarian/vegan, and gluten-free diets, were evaluated for their adequacy and potential benefits. The Mediterranean diet was highlighted for its protective effects against pregnancy-related health issues. In contrast, the review identified vegetarian and vegan diets as requiring careful planning to ensure sufficient intake of key nutrients. Additionally, the review explored the implications of gestational diabetes and dietary strategies for managing blood sugar levels. The effects of intermittent fasting during pregnancy were also discussed, with mixed evidence regarding its safety and impact on pregnancy outcomes. Overall, the review stresses the importance of tailored nutritional guidance to ensure optimal health for both the mother and the developing fetus during pregnancy and lactation.</div></div>","PeriodicalId":94141,"journal":{"name":"Metabolism open","volume":"25 ","pages":"Article 100353"},"PeriodicalIF":0.0,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143420746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-31DOI: 10.1016/j.metop.2025.100352
Gang Wei , Cheng Zhang , Feng-Jie Shen , Hua-Qi Guo , Lin Liu
Background
The causal relationship between the familial hypercholesterolemia (FH) and intestinal vascular diseases was unnoticed. This study aims to investigate the cause-and-effect relationship of FH with risk of intestinal vascular diseases in human.
Methods
A Mendelian randomization (MR) analysis was performed by extracting summary-level datasets for FH or FH concurrently with ischemic heart disease (IHD) and intestinal vascular diseases from the FinnGen study including 329,115, 316,290 and 350,505 individuals. The inverse-variance weighted (IVW) method and the weighted median method were applied to analyze the causal relationships between FH or FH concurrently with IHD and the risk of intestinal vascular diseases. Cochran's Q statistic method and MR-Egger regression were used to assess heterogeneity and pleiotropy.
Results
The IVW method demonstrated that FH was significantly associated with higher odds of intestinal vascular diseases [OR (95%CI): 1.22 (1.03, 1.45)] (P = 0.02) without significant heterogeneity (P = 0.54) and horizontal pleiotropy (P = 0.43). Rs7575840 in 6.5kda upstream of ApoB gene, rs11591147 in PCSK9 gene and rs9644862 in the CDKN2B-AS1 (or named ANRIL; p15AS; PCAT12; CDKN2BAS; CDKN2B-AS; NCRNA00089) gene were illustrated to mostly influence the risk of intestinal vascular diseases. However, no significant causal relationship between FH concurrently with IHD and intestinal vascular diseases was observed.
Conclusion
In conclusion, FH was causally positive-associated with the increased risk of intestinal vascular diseases, revealing a potential unfortunate outcome for FH. Therefore, patients with FH should pay closely attention to the risk of intestinal vascular diseases. Our study may provide evidence for new diagnostic and therapeutic strategies in clinical practices.
{"title":"Causal relationship of familial hypercholesterolemia with risk of intestinal vascular disorders: A mendelian randomization study","authors":"Gang Wei , Cheng Zhang , Feng-Jie Shen , Hua-Qi Guo , Lin Liu","doi":"10.1016/j.metop.2025.100352","DOIUrl":"10.1016/j.metop.2025.100352","url":null,"abstract":"<div><h3>Background</h3><div>The causal relationship between the familial hypercholesterolemia (FH) and intestinal vascular diseases was unnoticed. This study aims to investigate the cause-and-effect relationship of FH with risk of intestinal vascular diseases in human.</div></div><div><h3>Methods</h3><div>A Mendelian randomization (MR) analysis was performed by extracting summary-level datasets for FH or FH concurrently with ischemic heart disease (IHD) and intestinal vascular diseases from the FinnGen study including 329,115, 316,290 and 350,505 individuals. The inverse-variance weighted (IVW) method and the weighted median method were applied to analyze the causal relationships between FH or FH concurrently with IHD and the risk of intestinal vascular diseases. Cochran's Q statistic method and MR-Egger regression were used to assess heterogeneity and pleiotropy.</div></div><div><h3>Results</h3><div>The IVW method demonstrated that FH was significantly associated with higher odds of intestinal vascular diseases [OR (95%CI): 1.22 (1.03, 1.45)] (<em>P</em> = 0.02) without significant heterogeneity (<em>P</em> = 0.54) and horizontal pleiotropy (<em>P</em> = 0.43). Rs7575840 in 6.5kda upstream of <em>ApoB</em> gene, rs11591147 in <em>PCSK9</em> gene and rs9644862 in the <em>CDKN2B-AS1</em> (or named <em>ANRIL; p15AS</em>; <em>PCAT12</em>; <em>CDKN2BAS</em>; <em>CDKN2B-AS</em>; <em>NCRNA00089</em>) gene were illustrated to mostly influence the risk of intestinal vascular diseases. However, no significant causal relationship between FH concurrently with IHD and intestinal vascular diseases was observed.</div></div><div><h3>Conclusion</h3><div>In conclusion, FH was causally positive-associated with the increased risk of intestinal vascular diseases, revealing a potential unfortunate outcome for FH. Therefore, patients with FH should pay closely attention to the risk of intestinal vascular diseases. Our study may provide evidence for new diagnostic and therapeutic strategies in clinical practices.</div></div>","PeriodicalId":94141,"journal":{"name":"Metabolism open","volume":"25 ","pages":"Article 100352"},"PeriodicalIF":0.0,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143294267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Vitamin D plays a critical role in pregnancy, supporting placental function via angiogenesis, immune regulation, and nutrient transport. Deficiency in vitamin D during gestation is associated with complications such as preeclampsia, intrauterine growth restriction (IUGR), and preterm birth. However, the mechanisms linking vitamin D deficiency to placental dysfunction remain inadequately understood, highlighting the need for systematic evaluation.
Methods
A systematic review was conducted in adherence to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, with searches in PubMed, Scopus, and Web of Science for studies published within the last 20 years. Inclusion criteria targeted human studies examining the association between vitamin D and placental function, including randomized controlled trials, cohort studies, and case-control studies. A total of 10 studies were included following rigorous screening and quality assessment.
Results
Findings from human studies indicate that maternal vitamin D deficiency significantly impairs placental function by reducing vascular integrity, downregulating nutrient transporters, and promoting inflammation. Mechanistic evidence highlights decreased expression of vascular endothelial growth factor (VEGF) and increased inflammatory cytokines in vitamin D-deficient pregnancies. Supplementation with active vitamin D [1α,25(OH)2D3] mitigated these adverse effects, restoring placental growth, improving nutrient transport, and reducing inflammation. Notably, population-specific differences and sex-specific responses to vitamin D sufficiency were observed.
Conclusions
Vitamin D is essential for optimal placental function and pregnancy outcomes. This review underscores the need for standardized supplementation protocols and further research into long-term and population-specific effects of vitamin D. Addressing these gaps can inform targeted interventions to reduce pregnancy complications and improve maternal-fetal health.
维生素D在妊娠中起着至关重要的作用，通过血管生成、免疫调节和营养运输支持胎盘功能。妊娠期维生素D缺乏与子痫前期、宫内生长受限（IUGR）和早产等并发症有关。然而，将维生素D缺乏与胎盘功能障碍联系起来的机制仍然没有得到充分的了解，因此需要进行系统的评估。方法根据系统评价和荟萃分析（PRISMA）指南的首选报告项目进行系统评价，并在PubMed， Scopus和Web of Science中检索近20年发表的研究。纳入标准针对的是研究维生素D与胎盘功能之间关系的人类研究，包括随机对照试验、队列研究和病例对照研究。经过严格的筛选和质量评估，共纳入10项研究。结果人体研究结果表明，母体维生素D缺乏通过降低血管完整性、下调营养转运蛋白和促进炎症显著损害胎盘功能。机制证据强调在维生素d缺乏的妊娠中血管内皮生长因子（VEGF）的表达减少和炎症细胞因子的增加。补充活性维生素D [1α，25(OH)2D3]可以减轻这些不良反应，恢复胎盘生长，改善营养运输，减少炎症。值得注意的是，观察到人群特异性差异和对维生素D充足性的性别特异性反应。结论维生素D对优化胎盘功能和妊娠结局至关重要。这篇综述强调需要标准化的补充方案，并进一步研究维生素d的长期和人群特异性影响。解决这些差距可以为有针对性的干预提供信息，以减少妊娠并发症，改善母胎健康。
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Pub Date : 2025-01-30DOI: 10.1016/j.metop.2025.100351
Amina A. Alawadi , Amrita Vijay , Jane I. Grove , Moira A. Taylor , Guruprasad P. Aithal
Background
Metabolic dysfunction-Associated Steatotic Liver Disease (MASLD) affects up to one in five people in the UK, with persistent overeating and a sedentary lifestyle being significant risk factors. Exploring dietary patterns at a food level is a novel approach to understand associations between diet and disease.
Methods
This cross-sectional case-control study included 168 MASLD patients and 34 healthy controls from Nottingham (UK). Dietary data were collected using the EPIC-food frequency questionnaire. A food-group, tree classification method was developed which categorized 923 ingredients into three levels (main food group, sub-types, and cooking methods) and intakes were associated with clinical outcomes using logistic regression and degree of liver fibrosis using linear regression.
Results
Significant associations were found for red meat intake with MASLD (OR [CI]: 1.013 [1.001–1.025]) and fibrosis (Beta [SE]: +0.048 [0.013]); intakes of nuts (OR [CI]: 0.951 [0.905–0.999]); and fish (OR [CI]: 0.985 [0.971–0.999]) with MASLD; “Cereals and cereals products”, “salt and gravy” and baked foods with fibrosis (Beta [SE]: +0.018 to +0.057 [0.005–0.23]); white and organ meat (Beta [SE]: −0.04 to −0.61 [0.015–0.249]); diet soda (OR [CI]: +0.01 [1–1.003]) and red meat intakes (OR [CI]:+0.002 [1.002–1.016]) with T2DM; wholegrain wheat, red meat, and semi-skimmed dairy intakes with hypercholesterolemia (ORs [CI]: −0.003 to −0.023 [1–1.043]); “herbs and spices” and wholegrain rice with hypercholesterolaemia (ORs [CI]: −0.08 to −0.98 [0.159–0.989); fresh herbs and boiled foods intakes with hypertension (ORs [CI]: −0.001 to −2.21 [0.013–1]).
Conclusion
The study introduces a new food-group, tree classification method to characterise UK diet data and identify risk factors for MASLD, potentially informing the development of culturally applicable dietary guidelines designed to improve public health.
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