Metabolism open最新文献

{"title":"Clinical diagnosis, treatment, and genetic analysis of adolescent onset holocarboxylase synthetase deficiency and cobalamin C deficiency: A case report and literature review","authors":"Ye Ren ,&nbsp;Hongxing Dang ,&nbsp;Yueqiang Fu ,&nbsp;Chengjun Liu ,&nbsp;Jing Li ,&nbsp;Jinhua Cai","doi":"10.1016/j.metop.2025.100361","DOIUrl":"10.1016/j.metop.2025.100361","url":null,"abstract":"<div><h3>Background</h3><div>Holocarboxylase Synthetase Deficiency (HCSD) is an uncommon autosomal recessive genetic disorder that manifests with symptoms such as metabolic acidosis, lethargy, hypotonia, seizures, and persistent rashes, typically emerging during infancy. The HLCS gene has been identified as the source of pathogenic mutations associated with this condition. Cobalamin C (cblC) deficiency is another rare autosomal recessive disorder resulting from defects in cobalamin metabolism, attributable to mutations in the MMACHC gene. This disorder often leads to methylmalonic aciduria and homocystinuria and is classified into early-onset and late-onset types. The late-onset type is characterized by acute or chronic progressive neurological symptoms and behavioral disturbances. To date, there have been no documented cases worldwide of individuals diagnosed with both HCSD and cobalamin C deficiency.</div></div><div><h3>Case presentation</h3><div>This report details the case of an 11-year-and-9-month-old female patient from China who presented with symptoms including vomiting, altered consciousness, and a rash. Laboratory evaluations indicated the presence of metabolic acidosis, methylmalonic aciduria, and homocystinuria. Genetic analysis revealed mutations in the MMACHC gene: c.482G &gt; A (p.R161Q) and c.567dup (p.I190Yfs∗13). Additionally, two previously unreported mutations in the HLCS gene, c.1922G &gt; T (p.G641V) and c.1754C &gt; T (p.P585L), were identified. She was diagnosed with Holocarboxylase Synthetase Deficiency and Cobalamin C deficiency. The child showed significant improvement following treatment with hydroxocobalamin, betaine, and biotin.</div></div><div><h3>Conclusion</h3><div>This article reports a case of adolescent onset HCSD and cobalamin C deficiency. Treatment with hydroxocobalamin, betaine, and biotin is effective. Two novel mutations in the HLCS gene causative for HCSD have been reported, providing a broader foundation for mutational screening and offering insights into the diagnosis and treatment of similar disorders.</div></div>","PeriodicalId":94141,"journal":{"name":"Metabolism open","volume":"26 ","pages":"Article 100361"},"PeriodicalIF":0.0,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143704719","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}

{"title":"Association of blood manganese levels with non-alcoholic fatty liver disease in NHANES 2017–2020: A retrospective cross-sectional study","authors":"Qian Xue ,&nbsp;Hongju Chen","doi":"10.1016/j.metop.2025.100358","DOIUrl":"10.1016/j.metop.2025.100358","url":null,"abstract":"<div><h3>Objective</h3><div>This study investigates the link between blood manganese (Mn) levels and non-alcoholic fatty liver disease (NAFLD) in a U.S. adult population.</div></div><div><h3>Background</h3><div>The role of manganese in NAFLD remains poorly understood. However, the NHANES database offers valuable data on blood manganese levels and metabolic status for 6278 subjects in the United States, facilitating the study of this relationship.</div></div><div><h3>Methods</h3><div>To investigate the relationship between blood manganese (Mn) levels and NAFLD, we conducted a <em>t</em>-test to compare Mn levels between participants with and without NAFLD. Participants were categorized into quartiles based on their blood Mn levels. We then employed multiple logistic regression analysis and sensitivity analyses to further examine the Mn-NAFLD relationship.</div></div><div><h3>Results</h3><div>The NAFLD group had a significantly higher blood manganese level (10.0 ± 3.7 μg/L, P &lt; 0.05) than the control group. Stratifying 6278 subjects by blood manganese quartiles showed increased NAFLD odds in higher quartiles (Q2-Q4) vs. Q1 (ORs: 1.49, 1.37, 1.49). The Mn-NAFLD relationship followed an inverted L-shaped curve, peaking at 8.52 μg/L.</div></div><div><h3>Conclusions</h3><div>Elevated levels of manganese in the blood have been shown to be associated with an increase in the risk of NAFLD, and blood manganese values can be utilized as a marker for assessing NAFLD.</div></div>","PeriodicalId":94141,"journal":{"name":"Metabolism open","volume":"26 ","pages":"Article 100358"},"PeriodicalIF":0.0,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143704718","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}

{"title":"Celastrol targets CKB-mediated futile creatine cycle in human brown adipocytes thermogenesis","authors":"Jingyi Ni ,&nbsp;Baicheng Wang ,&nbsp;Xinyue Liu ,&nbsp;Rui Yin ,&nbsp;Jinlin Tang ,&nbsp;Siyu Hua ,&nbsp;Xiaoxiao Zhang ,&nbsp;Yangyang Wu ,&nbsp;Shihu Zhang ,&nbsp;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}

{"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 ,&nbsp;Christos S. Mantzoros ,&nbsp;Maya Rahme ,&nbsp;Rafic Baddoura ,&nbsp;Georges Halaby ,&nbsp;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/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. <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}

{"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 ,&nbsp;Lusine Gigoyan ,&nbsp;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 &lt; 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 &gt; 8, remote glucose monitoring use was associated with 0.93 % greater absolute improvement in HbA1c value (vs. non-users, p &lt; 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}

{"title":"SPT: A new contributor to trans fatty acid-induced atherosclerosis","authors":"Chengbin Li,&nbsp;Junli Liu,&nbsp;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}

{"title":"Lipidomics reveals potential biomarkers and pathophysiological insights in the progression of diabetic kidney disease","authors":"Xiaozhen Guo ,&nbsp;Zixuan Zhang ,&nbsp;Cuina Li ,&nbsp;Xueling Li ,&nbsp;Yutang Cao ,&nbsp;Yangyang Wang ,&nbsp;Jiaqi Li ,&nbsp;Yibin Wang ,&nbsp;Kanglong Wang ,&nbsp;Yameng Liu ,&nbsp;Cen Xie ,&nbsp;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}

{"title":"The role of lipoprotein sulfatides in MASLD fibrosis transition: A new frontier in hepatic immunomodulation","authors":"Yifan Zhou,&nbsp;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}

{"title":"An updated review of popular dietary patterns during pregnancy and lactation: Trends, benefits, and challenges","authors":"Maria Chouli ,&nbsp;Anastasia Bothou ,&nbsp;Giannoula Kyrkou ,&nbsp;Sofia Kaliarnta ,&nbsp;Aikaterini Dimitrakopoulou ,&nbsp;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}

{"title":"Causal relationship of familial hypercholesterolemia with risk of intestinal vascular disorders: A mendelian randomization study","authors":"Gang Wei ,&nbsp;Cheng Zhang ,&nbsp;Feng-Jie Shen ,&nbsp;Hua-Qi Guo ,&nbsp;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}