Yufeng Li, Zhun Shi, Xiuying Zhang, Huahui Ren, Hongyi Ji, Fangming Yang, Zuodi Fu, Xiangshuang Kong, Xiaoguang Cheng, Junhua Li, Kui Wu, Yiyi Zhong, Huanzi Zhong, Linong Ji
{"title":"Metagenomic analysis revealing links between age, gut microbiota and bone loss in Chinese adults.","authors":"Yufeng Li, Zhun Shi, Xiuying Zhang, Huahui Ren, Hongyi Ji, Fangming Yang, Zuodi Fu, Xiangshuang Kong, Xiaoguang Cheng, Junhua Li, Kui Wu, Yiyi Zhong, Huanzi Zhong, Linong Ji","doi":"10.1038/s44324-025-00060-7","DOIUrl":"10.1038/s44324-025-00060-7","url":null,"abstract":"<p><p>Accumulating evidence has linked gut microbiota to bone health. However, investigations into the impacts of aging, gut microbiota, and their interactions in the development of osteoporosis remain inconclusive. We employed quantitative computed tomography to measure lumbar bone mass density (BMD) and analyzed shotgun metagenomic data in 684 Chinese adults. Our analyses revealed significant positive associations between BMD and abundances of multiple Lachnospiraceae species, including Lachnospira eligens, Blautia wexlerae, and Roseburia hominis, as well as pathways involved in L-arginine biosynthesis and butyrate production-independent of age, diet habits, and lifestyles. Moreover, we demonstrated that individuals with enterotype Bacteroides exhibited a more pronounced age-related decline in BMD compared to those with enterotype Prevotella, a pattern we validated in an independent cohort. Our findings offer valuable insights into BMD-related gut microbial features and interactions between aging, gut microbiota, and bone loss, opening potential avenues for microbiota-based prevention and treatment strategies for osteoporosis.</p>","PeriodicalId":501710,"journal":{"name":"npj Metabolic Health and Disease","volume":"3 1","pages":"18"},"PeriodicalIF":0.0,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12118732/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144556406","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":"Comparison of polygenic risk scores for type 2 diabetes developed from different ancestry groups.","authors":"Takuma Furukawa, Megumi Hara, Yuichiro Nishida, Keitaro Tanaka, Chisato Shimanoe, Chiharu Iwasaka, Jun Otonari, Hiroaki Ikezaki, Mako Nagayoshi, Takashi Tamura, Yudai Tamada, Rieko Okada, Isao Oze, Hidemi Ito, Nobuaki Michihata, Yohko Nakamura, Shiroh Tanoue, Chihaya Koriyama, Sadao Suzuki, Takahiro Otani, Isao Watanabe, Satomi Tomida, Kiyonori Kuriki, Naoyuki Takashima, Aya Kadota, Masashi Ishizu, Takeshi Watanabe, Masahiro Nakatochi, Yukihide Momozawa, Kenji Wakai, Keitaro Matsuo","doi":"10.1038/s44324-025-00059-0","DOIUrl":"10.1038/s44324-025-00059-0","url":null,"abstract":"<p><p>Polygenic risk scores (PRS) are useful for assessing disease risk; however, knowledge about their effectiveness among Asian and other populations is limited. This study aimed to compare the classification accuracy of PRSs for type 2 diabetes (T2D-PRS) developed from different ancestry groups using genotype data from 14,083 Japanese participants. Participants' scores were calculated using T2D-PRS models, and logistic regression analysis and receiver operating characteristic curves were assessed. The odds ratio of diabetes per 1 standard deviation increase in PRS was 2.18 and 1.55 for the Japanese and European T2D-PRSs, respectively. The area under the curve (AUC) for the Japanese T2D-PRS was 0.781, whereas that for the European T2D-PRS was 0.738 (P < 0.001). Additionally, age-stratified analysis showed higher AUCs in younger than older age groups. The PRS developed from matched ancestry populations has high classification accuracy for diabetes and is particularly useful for the early detection of high-risk individuals with diabetes.</p>","PeriodicalId":501710,"journal":{"name":"npj Metabolic Health and Disease","volume":"3 1","pages":"17"},"PeriodicalIF":0.0,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12118717/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144556400","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}
Despina Kolivas, Liz Fraser, Ronald Schweitzer, Peter Brukner, George Moschonis
{"title":"mHealth low carbohydrate dietary intervention ameliorates glycaemic profile, blood pressure and weight status in people with type 2 diabetes.","authors":"Despina Kolivas, Liz Fraser, Ronald Schweitzer, Peter Brukner, George Moschonis","doi":"10.1038/s44324-025-00053-6","DOIUrl":"10.1038/s44324-025-00053-6","url":null,"abstract":"<p><p>Low carbohydrate diets (LCD) have shown efficacy in managing clinical outcomes in type 2 diabetes (T2D). Incorporating digital tools into health care provides an adjunct treatment modality, to educate patients and provide clinical support. This study examines the effect of a mobile health (mHealth) LCD application (app) on glycaemic profile, blood pressure and weight status, in people with T2D. The study is an online single-arm, pre-post study that recruited people with T2D from around Australia, referred via registered supporting general practitioners (GPs). The intervention (Defeat Diabetes app) provides education and resources on the use of a LCD for ongoing management of T2D. After 3 months, our cohort of 99 participants (mean age 59 ± 11 years, 55 females) showed reduced dietary carbohydrate intake as a proportion of overall energy (-14%kJ/day, 95% CI: -17 to -11). Improvement in the primary outcome HbA1c (-1.0%, 95% CI: -1.3 to -0.7), was associated with reduction in dietary carbohydrate intake. Systolic blood pressure (SBP) improved (-6 mmHg, 95% CI: -10 to -1), while 21 participants reduced their diabetes medication dose with two participants discontinuing all diabetes medication. These findings demonstrate that people with T2D receiving LCD education and resources through the Defeat Diabetes app for 3 months improved their glycaemic profile and SBP despite decreased overall medication usage in almost one third of the study sample prescribed medication at baseline.</p>","PeriodicalId":501710,"journal":{"name":"npj Metabolic Health and Disease","volume":"3 1","pages":"12"},"PeriodicalIF":0.0,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12118682/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144556407","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":"Longitudinal association of metabolic dysfunction-associated fatty liver disease, serum metabolites, with cognitive function trajectories.","authors":"Anxin Wang, Xue Tian, Qiqi Deng, Manqi Zheng, Xue Xia, Yijun Zhang, Yan Tan, Qian Hua","doi":"10.1038/s44324-025-00055-4","DOIUrl":"10.1038/s44324-025-00055-4","url":null,"abstract":"<p><p>This study examined the longitudinal association of metabolic dysfunction-associated fatty liver disease (MAFLD) with distinct cognitive function trajectories, and determine whether and to what extent this association was mediated by MAFLD-related metabolites among 845 participants. Two cognitive function trajectories were identified as normal (n = 714, 84.50%) or large decrease (n = 131, 15.50%) pattern over 7 years. Participants with MAFLD (N = 277, 32.78%) had an 81% higher risk of developing a large decrease in cognitive function (odds ratio, 1.81; 95% confidence interval, 1.16-2.94) than non-MAFLD. Three MAFLD-related metabolites were identified as lysoPC(20:3(5z,8z,11z)), lysoPE(18:1(9z)/0:0), and valine, of which lysoPE(18:1(9z)/0:0) and valine played a partially mediated role in the association of MAFLD with a large decrease in cognitive function (mediation proportion = 9.93% and 11.04%, respectively). The results indicated that MAFLD was associated with a higher risk of developing a large decrease in cognitive function, which was partially mediated by lipid and amino acid metabolism.</p>","PeriodicalId":501710,"journal":{"name":"npj Metabolic Health and Disease","volume":"3 1","pages":"11"},"PeriodicalIF":0.0,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12118734/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144556404","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":"Myeloid ACAT1/SOAT1: a novel regulator of dyslipidemia and retinal neovascularization.","authors":"Syed A H Zaidi, Ruth B Caldwell, Modesto A Rojas","doi":"10.1038/s44324-024-00046-x","DOIUrl":"10.1038/s44324-024-00046-x","url":null,"abstract":"<p><p>Pathological retinal neovascularization (RNV) is a major cause of vision loss and blindness during ischemic retinopathies. Our investigations in the mouse model of oxygen-induced retinopathy (OIR) demonstrate a novel mechanism of pathological RNV and neurovascular injury. We show that OIR-induced activation of macrophage/microglial cells, retinal inflammation, and pathological RNV are mediated by increases in cholesterol ester (CE) formation due to activation of the acyl-CoA: Cholesterol Acyltransferase 1/Sterol O-Acyltransferase 1 (ACAT1/SOAT1) enzyme.</p>","PeriodicalId":501710,"journal":{"name":"npj Metabolic Health and Disease","volume":"3 1","pages":"2"},"PeriodicalIF":0.0,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12091695/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144556408","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":"RNA-binding proteins as versatile metabolic regulators.","authors":"Ellie Koletsou, Ina Huppertz","doi":"10.1038/s44324-024-00044-z","DOIUrl":"10.1038/s44324-024-00044-z","url":null,"abstract":"<p><p>Metabolic shifts are a hallmark of numerous biological processes, including the differentiation of stem cells along a specific lineage and the activation of diverse cell types, such as immune cells. This review examines the intricate energy metabolic alterations that occur in diverse biological settings, from embryonic development to adult tissue homoeostasis and disease states. In particular, we emphasise the regulatory function of RNA-binding proteins (RBPs) in coordinating these metabolic shifts and examine how they modulate key pathways, such as glycolysis and oxidative phosphorylation, to meet the dynamic cellular energy demands. This review highlights the various mechanisms by which RBPs regulate these changes, ranging from active involvement in the post-transcriptional regulation of metabolically relevant genes to alteration of an RBP's function by specific RNAs, metabolites or growth factors. Finally, we consider how ageing and disease affect the function of RBPs and how RBPs can disrupt the delicate balance of metabolic regulation. Taken together, this review provides a comprehensive overview of the critical interplay between RBPs and metabolism and offers insights into potential therapeutic targets for regenerative medicine and age-related diseases.</p>","PeriodicalId":501710,"journal":{"name":"npj Metabolic Health and Disease","volume":"3 1","pages":"1"},"PeriodicalIF":0.0,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12091694/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144556410","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":"Regulation of gene expression through protein-metabolite interactions.","authors":"Maximilian Hornisch, Ilaria Piazza","doi":"10.1038/s44324-024-00047-w","DOIUrl":"10.1038/s44324-024-00047-w","url":null,"abstract":"<p><p>Organisms have to adapt to changes in their environment. Cellular adaptation requires sensing, signalling and ultimately the activation of cellular programs. Metabolites are environmental signals that are sensed by proteins, such as metabolic enzymes, protein kinases and nuclear receptors. Recent studies have discovered novel metabolite sensors that function as gene regulatory proteins such as chromatin associated factors or RNA binding proteins. Due to their function in regulating gene expression, metabolite-induced allosteric control of these proteins facilitates a crosstalk between metabolism and gene expression. Here we discuss the direct control of gene regulatory processes by metabolites and recent progresses that expand our abilities to systematically characterize metabolite-protein interaction networks. Obtaining a profound map of such networks is of great interest for aiding metabolic disease treatment and drug target identification.</p>","PeriodicalId":501710,"journal":{"name":"npj Metabolic Health and Disease","volume":"3 1","pages":"7"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11879850/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143575043","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}
Fivos Borbolis, Christina Ploumi, Konstantinos Palikaras
{"title":"Calcium-mediated regulation of mitophagy: implications in neurodegenerative diseases.","authors":"Fivos Borbolis, Christina Ploumi, Konstantinos Palikaras","doi":"10.1038/s44324-025-00049-2","DOIUrl":"10.1038/s44324-025-00049-2","url":null,"abstract":"<p><p>Calcium signaling plays a pivotal role in diverse cellular processes through precise spatiotemporal regulation and interaction with effector proteins across distinct subcellular compartments. Mitochondria, in particular, act as central hubs for calcium buffering, orchestrating energy production, redox balance and apoptotic signaling, among others. While controlled mitochondrial calcium uptake supports ATP synthesis and metabolic regulation, excessive accumulation can trigger oxidative stress, mitochondrial membrane permeabilization, and cell death. Emerging findings underscore the intricate interplay between calcium homeostasis and mitophagy, a selective type of autophagy for mitochondria elimination. Although the literature is still emerging, this review delves into the bidirectional relationship between calcium signaling and mitophagy pathways, providing compelling mechanistic insights. Furthermore, we discuss how disruptions in calcium homeostasis impair mitophagy, contributing to mitochondrial dysfunction and the pathogenesis of common neurodegenerative diseases.</p>","PeriodicalId":501710,"journal":{"name":"npj Metabolic Health and Disease","volume":"3 1","pages":"4"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11790495/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143257769","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}
Filip Morys, Arsene Kanyamibwa, Daniel Fängström, Max Tweedale, Alexandre Pastor-Bernier, Houman Azizi, Lang Liu, Annette Horstmann, Alain Dagher
{"title":"Ultra-processed food consumption affects structural integrity of feeding-related brain regions independent of and via adiposity.","authors":"Filip Morys, Arsene Kanyamibwa, Daniel Fängström, Max Tweedale, Alexandre Pastor-Bernier, Houman Azizi, Lang Liu, Annette Horstmann, Alain Dagher","doi":"10.1038/s44324-025-00056-3","DOIUrl":"https://doi.org/10.1038/s44324-025-00056-3","url":null,"abstract":"<p><p>Consumption of ultra-processed foods (UPFs) increases overall caloric intake and is associated with obesity, cardiovascular disease, and brain pathology. There is scant evidence as to why UPF consumption leads to increased caloric intake and whether the negative health consequences are due to adiposity or characteristics of UPFs. Using the UK Biobank sample, we probed the associations between UPF consumption, adiposity, metabolism, and brain structure. Our analysis reveals that high UPF intake is linked to adverse adiposity and metabolic profiles, alongside cellularity changes in feeding-related subcortical brain areas. These are partially mediated by dyslipidemia, systemic inflammation and body mass index, suggesting that UPFs exert effects on the brain beyond just contributing to obesity. This dysregulation of the network of subcortical feeding-related brain structures may create a self-reinforcing cycle of increased UPF consumption.</p>","PeriodicalId":501710,"journal":{"name":"npj Metabolic Health and Disease","volume":"3 1","pages":"13"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11978510/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144035572","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":"Pulling back the mitochondria's iron curtain.","authors":"Shani Ben Zichri-David, Liraz Shkuri, Tslil Ast","doi":"10.1038/s44324-024-00045-y","DOIUrl":"10.1038/s44324-024-00045-y","url":null,"abstract":"<p><p>Mitochondrial functionality and cellular iron homeostasis are closely intertwined. Mitochondria are biosynthetic hubs for essential iron cofactors such as iron-sulfur (Fe-S) clusters and heme. These cofactors, in turn, enable key mitochondrial pathways, such as energy and metabolite production. Mishandling of mitochondrial iron is associated with a spectrum of human pathologies ranging from rare genetic disorders to common conditions. Here, we review mitochondrial iron utilization and its intersection with disease.</p>","PeriodicalId":501710,"journal":{"name":"npj Metabolic Health and Disease","volume":"3 1","pages":"6"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11879881/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143575041","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}