Accurate measurement of dietary intake remains a cornerstone challenge in optimizing the efficacy of nutritional interventions in human disease. Traditional self-reporting methods, although scalable and widely used, are prone to major bias and measurement error, thereby limiting their precision and clinical utility. In this Review, we highlight recent advances in technology-assisted food intake measurement, including image-based logging, wearable sensors and artificial intelligence (AI)-based dietary estimation, which may reduce reliance on recall and improve intake estimation. We review the emergence of non-invasive biological methodologies, such as metagenome-informed metaproteomics, in accurately enabling objective measurement of food intake and nutrient digestion and absorption in molecular resolution. We explore the possible interactions and effects of the gut microbiome in modulating such person-specific digestive and absorptive patterns and discuss challenges and prospects in the convergence of omics-based, measurement-based and AI-based dietary assessment tools into precision nutrition, in fulfilling its immense potential towards optimization of patient care.
{"title":"Advances and opportunities in measuring dietary intake: from omics to AI.","authors":"Yotam Cohen,Tallulah Jansen,Serena Onwuka,Eran Elinav","doi":"10.1038/s42255-026-01494-z","DOIUrl":"https://doi.org/10.1038/s42255-026-01494-z","url":null,"abstract":"Accurate measurement of dietary intake remains a cornerstone challenge in optimizing the efficacy of nutritional interventions in human disease. Traditional self-reporting methods, although scalable and widely used, are prone to major bias and measurement error, thereby limiting their precision and clinical utility. In this Review, we highlight recent advances in technology-assisted food intake measurement, including image-based logging, wearable sensors and artificial intelligence (AI)-based dietary estimation, which may reduce reliance on recall and improve intake estimation. We review the emergence of non-invasive biological methodologies, such as metagenome-informed metaproteomics, in accurately enabling objective measurement of food intake and nutrient digestion and absorption in molecular resolution. We explore the possible interactions and effects of the gut microbiome in modulating such person-specific digestive and absorptive patterns and discuss challenges and prospects in the convergence of omics-based, measurement-based and AI-based dietary assessment tools into precision nutrition, in fulfilling its immense potential towards optimization of patient care.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"20 1","pages":""},"PeriodicalIF":20.8,"publicationDate":"2026-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147478898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-12DOI: 10.1038/s42255-026-01475-2
Ibrahim AlZaim, Mohamed N. Hassan, Maja Schröter, Luca Mannino, Katarina Dragicevic, Marie Balle Sjogaard, Joseph Festa, Lolita Dokshokova, Sophie Weinbrenner, Blanca Tardajos Ayllon, Bettina Hansen, Rikke Kongsgaard Rasmussen, Julie N. Christensen, Olivia Wagman, Ruby Schipper, Min Cai, Wouter Dheedene, Anja Bille Bohn, Jean Farup, Lin Lin, Samuele Soraggi, Anna Dalsgaard Thorsen, Amanda Bæk, Henrik Holm Thomsen, Maximilian von Heesen, Lena-Christin Conradi, Paul Evans, Carolina E. Hagberg, Joerg Heeren, Margo Emont, Evan D. Rosen, Aernout Luttun, Anders Etzerodt, Lucas Massier, Mikael Rydén, Niklas Mejhert, Matthias Blüher, Konstantin Khodosevich, Robert A. Fenton, Bilal N. Sheikh, Niels Jessen, Laura P.M.H. de Rooij, Joanna Kalucka
Adipose tissue homeostasis depends on an intact vascular network that ensures adequate nutrient delivery and immune regulation. In obesity, vascular dysfunction, particularly within endothelial cells (ECs), contributes to inflammation and metabolic disease progression, yet the cellular organization of the human adipose vasculature remains poorly defined. Here we show, using single-cell RNA sequencing of nearly 70,000 vascular cells from human subcutaneous adipose tissue of 65 individuals, that the adipose vasculature is highly heterogeneous and consists of seven canonical EC subtypes. In addition, we identify a distinct population of ECs that display mixed endothelial, mesenchymal, adipocytic and immune transcriptional features. Computational analyses and whole-mount imaging support their presence and suggest that they emerge through endothelial-to-mesenchymal transition. Comparative analyses further reveal inflammatory and fibrotic vascular signatures in obesity and type 2 diabetes. Together, this atlas delineates the cellular complexity of the human adipose vasculature and highlights its contribution to metabolic disease.
{"title":"Defining the vascular niche of human adipose tissue across metabolic states","authors":"Ibrahim AlZaim, Mohamed N. Hassan, Maja Schröter, Luca Mannino, Katarina Dragicevic, Marie Balle Sjogaard, Joseph Festa, Lolita Dokshokova, Sophie Weinbrenner, Blanca Tardajos Ayllon, Bettina Hansen, Rikke Kongsgaard Rasmussen, Julie N. Christensen, Olivia Wagman, Ruby Schipper, Min Cai, Wouter Dheedene, Anja Bille Bohn, Jean Farup, Lin Lin, Samuele Soraggi, Anna Dalsgaard Thorsen, Amanda Bæk, Henrik Holm Thomsen, Maximilian von Heesen, Lena-Christin Conradi, Paul Evans, Carolina E. Hagberg, Joerg Heeren, Margo Emont, Evan D. Rosen, Aernout Luttun, Anders Etzerodt, Lucas Massier, Mikael Rydén, Niklas Mejhert, Matthias Blüher, Konstantin Khodosevich, Robert A. Fenton, Bilal N. Sheikh, Niels Jessen, Laura P.M.H. de Rooij, Joanna Kalucka","doi":"10.1038/s42255-026-01475-2","DOIUrl":"https://doi.org/10.1038/s42255-026-01475-2","url":null,"abstract":"Adipose tissue homeostasis depends on an intact vascular network that ensures adequate nutrient delivery and immune regulation. In obesity, vascular dysfunction, particularly within endothelial cells (ECs), contributes to inflammation and metabolic disease progression, yet the cellular organization of the human adipose vasculature remains poorly defined. Here we show, using single-cell RNA sequencing of nearly 70,000 vascular cells from human subcutaneous adipose tissue of 65 individuals, that the adipose vasculature is highly heterogeneous and consists of seven canonical EC subtypes. In addition, we identify a distinct population of ECs that display mixed endothelial, mesenchymal, adipocytic and immune transcriptional features. Computational analyses and whole-mount imaging support their presence and suggest that they emerge through endothelial-to-mesenchymal transition. Comparative analyses further reveal inflammatory and fibrotic vascular signatures in obesity and type 2 diabetes. Together, this atlas delineates the cellular complexity of the human adipose vasculature and highlights its contribution to metabolic disease.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"26 1","pages":""},"PeriodicalIF":20.8,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147394039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tissue regeneration is essential for maintaining tissue homoeostasis and influences disease progression. In the liver, injury evokes a complex regenerative response with robust immune activation and metabolic rewiring, yet how these processes coordinate hepatocyte proliferation remains unclear. Here we show the presence of an injury-induced, lipid-dependent accrual of a distinct monocyte-derived macrophage (MDM) subset characterized by abundant cytosolic lipid content and heightened inflammatory response. Multi-omic analyses, spanning both single-cell transcriptomics and quantitative lipidomics, unveil substantial cellular diversity and heterogeneity between these 'lipo-inflammatory MDMs' (termed LIMMs) and other hepatic macrophages, including Kupffer cells. Blocking CD36-dependent LIMM induction markedly impairs hepatocyte proliferation and liver regeneration in injured livers. Mechanistically, CD36-mediated increase in ceramide biosynthesis activates IRE1α-XBP1 signalling pathway in LIMMs, driving production of the regenerative cytokine interleukin-6. Disrupting CD36-dependent IRE1α activation in LIMMs compromises liver repair. These findings identify a lipid-laden MDM subcluster as a key regulator of regenerative inflammation in injured livers.
{"title":"Lipid-dependent accrual of a subset of monocyte-derived macrophages is essential for tissue regeneration.","authors":"Tao Yao,Xin Tian,Linbin Rao,Jinling Ni,Jiayong Yu,Hongguo Yang,Yuexiao Tang,Xingxiao Huang,Xintong Xia,Lin Zhao,Bowen Diao,Yan Ping,Danni Wei,Siqi Li,Hui Chai,Zhiming Hu,Xiongzhong Ruan,Suihan Feng,Mengle Shao,Bo Shan,Ying Wu","doi":"10.1038/s42255-026-01480-5","DOIUrl":"https://doi.org/10.1038/s42255-026-01480-5","url":null,"abstract":"Tissue regeneration is essential for maintaining tissue homoeostasis and influences disease progression. In the liver, injury evokes a complex regenerative response with robust immune activation and metabolic rewiring, yet how these processes coordinate hepatocyte proliferation remains unclear. Here we show the presence of an injury-induced, lipid-dependent accrual of a distinct monocyte-derived macrophage (MDM) subset characterized by abundant cytosolic lipid content and heightened inflammatory response. Multi-omic analyses, spanning both single-cell transcriptomics and quantitative lipidomics, unveil substantial cellular diversity and heterogeneity between these 'lipo-inflammatory MDMs' (termed LIMMs) and other hepatic macrophages, including Kupffer cells. Blocking CD36-dependent LIMM induction markedly impairs hepatocyte proliferation and liver regeneration in injured livers. Mechanistically, CD36-mediated increase in ceramide biosynthesis activates IRE1α-XBP1 signalling pathway in LIMMs, driving production of the regenerative cytokine interleukin-6. Disrupting CD36-dependent IRE1α activation in LIMMs compromises liver repair. These findings identify a lipid-laden MDM subcluster as a key regulator of regenerative inflammation in injured livers.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"18 1","pages":""},"PeriodicalIF":20.8,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147393971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-05DOI: 10.1038/s42255-026-01474-3
Yuna Choi, Min Woo Kim, Gyeongyun Go, Dongsheng Cai
The hypothalamus regulates feeding and metabolic balance in response to metabolic cues. Here we report that extracellular vesicles (EVs) are secreted from the mediobasal hypothalamus in a diurnal manner that is influenced by daily feeding. Sox2-positive tanycytes have a critical role in maintaining the diurnal pattern of hypothalamic EV release. Inhibition of tanycyte EV release leads to a loss of feeding diurnality, weight control and blood glucose homoeostasis, whereas supplementation with tanycytic EVs confers metabolic benefits. We show that a subset of tanycytic EVs carries surface prepro-insulin (ppIns), which mediates recognition and uptake by insulin-receptor-positive hypothalamic neurons. These EVs are loaded with mTORC components, including Rictor in a low-phosphorylation state, and support hypothalamic neuronal signalling. Both ppIns and Rictor are important for the EV-mediated preservation of feeding rhythmicity and resistance to diet-induced metabolic dysfunction. Collectively, these findings identify tanycyte-derived EVs as regulators of feeding diurnality through insulin precursor-directed targeting and delivery of mTORC components to hypothalamic neurons.
{"title":"Metabolic regulation by tanycyte-derived extracellular vesicles through insulin precursor-mediated neuronal recognition and mTORC component delivery","authors":"Yuna Choi, Min Woo Kim, Gyeongyun Go, Dongsheng Cai","doi":"10.1038/s42255-026-01474-3","DOIUrl":"https://doi.org/10.1038/s42255-026-01474-3","url":null,"abstract":"The hypothalamus regulates feeding and metabolic balance in response to metabolic cues. Here we report that extracellular vesicles (EVs) are secreted from the mediobasal hypothalamus in a diurnal manner that is influenced by daily feeding. Sox2-positive tanycytes have a critical role in maintaining the diurnal pattern of hypothalamic EV release. Inhibition of tanycyte EV release leads to a loss of feeding diurnality, weight control and blood glucose homoeostasis, whereas supplementation with tanycytic EVs confers metabolic benefits. We show that a subset of tanycytic EVs carries surface prepro-insulin (ppIns), which mediates recognition and uptake by insulin-receptor-positive hypothalamic neurons. These EVs are loaded with mTORC components, including Rictor in a low-phosphorylation state, and support hypothalamic neuronal signalling. Both ppIns and Rictor are important for the EV-mediated preservation of feeding rhythmicity and resistance to diet-induced metabolic dysfunction. Collectively, these findings identify tanycyte-derived EVs as regulators of feeding diurnality through insulin precursor-directed targeting and delivery of mTORC components to hypothalamic neurons.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"227 1","pages":""},"PeriodicalIF":20.8,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147351034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-04DOI: 10.1038/s42255-026-01490-3
{"title":"Weighing in on the incretin revolution.","authors":"","doi":"10.1038/s42255-026-01490-3","DOIUrl":"https://doi.org/10.1038/s42255-026-01490-3","url":null,"abstract":"","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"98 1","pages":""},"PeriodicalIF":20.8,"publicationDate":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147351090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kirsten rat sarcoma (KRAS) mutations are key drivers of oncogenesis and therapy resistance in colorectal cancer (CRC), yet the underlying molecular mechanisms and effective targeted therapies are currently limited. Here we identify thyroid hormone receptor interactor 6 (TRIP6) phosphorylation as a critical mechanism of immune evasion in KRAS-mutant (KRAS/MT) CRC. In KRAS wild-type CRC cells, unphosphorylated TRIP6 binds to KDM1A, repressing enolase 2 (ENO2) expression via H3K9me1/H3K9me2 accumulation and limiting glycolysis. In KRAS/MT CRC cells, ERK1/ERK2-mediated phosphorylation of TRIP6 disrupts this interaction, enhancing ENO2-driven glycolysis and lactate production. Elevated extracellular lactate promotes CD44 lactylation on CD8+ T cells, impairs hyaluronan binding and AKT signalling, and ultimately suppresses anti-tumour immunity. Blocking TRIP6 phosphorylation with the peptide mouse PT6 restores T cell function and improves response to anti-PD-1 therapy in preclinical models. Collectively, our findings reveal a new mechanism of immune evasion in KRAS/MT CRC and suggest that targeting the TRIP6–ENO2–CD44 lactylation axis could be a promising strategy to overcome resistance to immunotherapy.
{"title":"Extracellular CD44 lactylation impairs CD8+ T cell function in KRAS-mutant colorectal cancer","authors":"Yun Yang, Yong Wu, Xin Guo, Wen-Juan Gan, Wen-Xin Wu, Wei-Yi Shi, Xiao-Shun He, Yi-Xuan Liu, Shan Wan, Zhi Jiang, Yue Liu, Xiu-Ming Li, Zu-Da Pan, Xue Zhang, You Xu, Xiao-Jiao Gao, Ling-Chuan Guo, Guideng Li, Hua Wu","doi":"10.1038/s42255-026-01482-3","DOIUrl":"https://doi.org/10.1038/s42255-026-01482-3","url":null,"abstract":"Kirsten rat sarcoma (KRAS) mutations are key drivers of oncogenesis and therapy resistance in colorectal cancer (CRC), yet the underlying molecular mechanisms and effective targeted therapies are currently limited. Here we identify thyroid hormone receptor interactor 6 (TRIP6) phosphorylation as a critical mechanism of immune evasion in KRAS-mutant (KRAS/MT) CRC. In KRAS wild-type CRC cells, unphosphorylated TRIP6 binds to KDM1A, repressing enolase 2 (ENO2) expression via H3K9me1/H3K9me2 accumulation and limiting glycolysis. In KRAS/MT CRC cells, ERK1/ERK2-mediated phosphorylation of TRIP6 disrupts this interaction, enhancing ENO2-driven glycolysis and lactate production. Elevated extracellular lactate promotes CD44 lactylation on CD8+ T cells, impairs hyaluronan binding and AKT signalling, and ultimately suppresses anti-tumour immunity. Blocking TRIP6 phosphorylation with the peptide mouse PT6 restores T cell function and improves response to anti-PD-1 therapy in preclinical models. Collectively, our findings reveal a new mechanism of immune evasion in KRAS/MT CRC and suggest that targeting the TRIP6–ENO2–CD44 lactylation axis could be a promising strategy to overcome resistance to immunotherapy.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"144 1","pages":""},"PeriodicalIF":20.8,"publicationDate":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147346879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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