Nature metabolism最新文献

{"title":"Author Correction: The sphingosine-1-phosphate receptor 1 mediates the atheroprotective effect of eicosapentaenoic acid","authors":"Ting Zhou, Jie Cheng, Shuo He, Chao Zhang, Ming-Xin Gao, Li-Jun Zhang, Jin-Peng Sun, Yi Zhu, Ding Ai","doi":"10.1038/s42255-025-01335-5","DOIUrl":"10.1038/s42255-025-01335-5","url":null,"abstract":"","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"7 8","pages":"1714-1714"},"PeriodicalIF":20.8,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s42255-025-01335-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Upper-gastrointestinal tract metabolite profile regulates glycaemic and satiety responses to meals with contrasting structure: a pilot study","authors":"Mingzhu Cai, Shilpa Tejpal, Martina Tashkova, Peter Ryden, Natalia Perez-Moral, Shikha Saha, Isabel Garcia-Perez, Jose Ivan Serrano Contreras, Julien Wist, Elaine Holmes, Andres Bernal, Bowen Dou, Georgia Franco Becker, Gary Frost, Cathrina Edwards","doi":"10.1038/s42255-025-01309-7","DOIUrl":"10.1038/s42255-025-01309-7","url":null,"abstract":"Dietary interventions to combat non-communicable diseases focus on optimizing food intake but overlook the influence of food structure. Here, we investigate how food structure influences digestion. In a randomized crossover study, ten healthy participants were fitted with nasoenteric tubes that allow simultaneous gastric and duodenal sampling, before consuming iso-nutrient chickpea meals with contrasting cellular structures. The primary outcome is gut hormone response. Secondary outcomes are intestinal content analysis, blood glucose and insulin response, subjective appetite changes and ad libitum energy intake. We show that the ‘Broken’ and ‘Intact’ cell structures of meals result in different digestive and metabolomic profiles, leading to distinct postprandial gut hormones, glycaemia and satiety responses. ‘Broken’ meal structure elicits higher glucose-dependent insulinotropic peptide, glucagon-like peptide-1 and blood glycaemia, driven by high starch digestibility and a sharp rise in gastric maltose within 30 min. ‘Intact’ meal structure produces a prolonged release of glucagon-like peptide-1 and peptide-YY, elevated duodenal amino acids and undigested starch at 120 min. This work highlights how food structure alters upper gastrointestinal nutrient-sensing hormones, providing insights into the adverse effects of modern diets on obesity and type 2 diabetes. ISRCTN registration: ISRCTN18097249. In this randomized crossover pilot study, the authors collected human gastrointestinal digesta using a unique intubation technique to compare how meals with contrasting cellular structures affect postprandial luminal metabolites, glycaemia, gut hormones and satiety sensation.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"7 7","pages":"1459-1475"},"PeriodicalIF":20.8,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s42255-025-01309-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144329041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A brief guide to statistical analysis of grouped data in preclinical research","authors":"Colby J. Vorland, Lilian Golzarri-Arroyo, David B. Allison","doi":"10.1038/s42255-025-01323-9","DOIUrl":"10.1038/s42255-025-01323-9","url":null,"abstract":"Clustering and nesting (C&N) arise in many preclinical studies, such as when animals are group-housed or share litters, or in cell culture. Ignoring C&N undermines the validity of analyses. Here, we explain how C&N arise, as well as valid designs and analyses.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"7 7","pages":"1301-1304"},"PeriodicalIF":20.8,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144329037","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}

{"title":"A nitroalkene derivative of salicylate, SANA, induces creatine-dependent thermogenesis and promotes weight loss","authors":"Karina Cal, Alejandro Leyva, Jorge Rodríguez-Duarte, Santiago Ruiz, Leonardo Santos, Maria Pia Garat, Lucía Colella, Mariana Ingold, Andrés Benitez-Rosendo, Valentina Pérez-Torrado, Cecilia Vilaseca, German Galliussi, Lucía Ziegler, Thais R. Peclat, Mariana Bresque, Rachel M. Handy, Rachel King, Larissa Menezes dos Reis, João Manoel Alves, Camila Espasandín, Victoria de la Sovera, Peter Breining, Rosina Dapueto, Andrés Lopez, Katie L. Thompson, Caroline A. Lino, Julia V. França, Thayna S. Vieira, Ramandeep Rattan, Guillermo Agorrody, Evan DeVallance, Jacqueline Haag, Ethan Meadows, Sara E. Lewis, Gabriele Catarine Santana Barbosa, Leonardo Osbourne Lai de Souza, Marina Santos Chichierchio, Valeria Valez, Adrián Aicardo, Paola Contreras, Mikkel H. Vendelbo, Steen Jakobsen, Andrés Kamaid, Williams Porcal, Aldo Calliari, José Manuel Verdes, Jianhai Du, Yekai Wang, John M. Hollander, Thomas A. White, Rafael Radi, Guillermo Moyna, Celia Quijano, Robert O’Doherty, Pedro Moraes-Vieira, Shailendra Giri, Graham P. Holloway, William T. Festuccia, Luiz Osório Leiria, Roberta Leonardi, Marcelo A. Mori, Juliana Camacho-Pereira, Eric E. Kelley, Rosario Duran, Gloria V. López, Eduardo N. Chini, Carlos Batthyány, Carlos Escande","doi":"10.1038/s42255-025-01311-z","DOIUrl":"10.1038/s42255-025-01311-z","url":null,"abstract":"The emergence of glucagon-like peptide-1 agonists represents a notable advancement in the pharmacological treatment of obesity, yet complementary approaches are essential. Through phenotypic drug discovery, we developed promising nitroalkene-containing small molecules for obesity-related metabolic dysfunctions. Here, we present SANA, a nitroalkene derivative of salicylate, demonstrating notable efficacy in preclinical models of diet-induced obesity. SANA reduces liver steatosis and insulin resistance by enhancing mitochondrial respiration and increasing creatine-dependent energy expenditure in adipose tissue, functioning effectively in thermoneutral conditions and independently of uncoupling protein 1 and AMPK activity. Finally, we conducted a randomized, double-blind, placebo-controlled phase 1A/B clinical trial, which consisted of two parts, each with four arms: (A) single ascending doses (200–800 mg) in healthy lean volunteers; (B) multiple ascending doses (200–400 mg per day for 15 days) in healthy volunteers with overweight or obesity. The primary endpoint assessed safety and tolerability. Secondary and exploratory endpoints included pharmacokinetics, tolerability, body weight and metabolic markers. SANA shows good safety and tolerability, and demonstrates beneficial effects on body weight and glucose management within 2 weeks of treatment. Overall, SANA appears to be a first-in-class activator of creatine-dependent energy expenditure and thermogenesis, highlighting its potential as a therapeutic candidate for ‘diabesity’. Australian New Zealand Clinical Trials Registry registration: ACTRN12622001519741 . In this study, the authors describe SANA, a nitroalkene derivative of salicylate, as a potential activator of creatine-dependent energy expenditure and thermogenesis in adipose tissue. Preclinical and clinical data from this paper also suggest that SANA improves glucose homeostasis and promotes weight loss in mice and humans.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"7 8","pages":"1550-1569"},"PeriodicalIF":20.8,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s42255-025-01311-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144311476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A food-sensitive olfactory circuit drives anticipatory satiety","authors":"Janice Bulk, Joscha N. Schmehr, Tobias Ackels, Rui de Oliveira Beleza, André Carvalho, Ayden Gouveia, Lionel Rigoux, Vincent Hellier, Anna Lena Cremer, Heiko Backes, Andreas Schaefer, Sophie M. Steculorum","doi":"10.1038/s42255-025-01301-1","DOIUrl":"10.1038/s42255-025-01301-1","url":null,"abstract":"Food sensory perception has emerged as a potent regulator of specialized feeding circuits; yet, the consequences on feeding behaviour and the underlying neuronal basis remain poorly understood. Here, we reveal a sensory pathway that co-ordinately integrates food odours to control forthcoming nutrient intake in male mice. Unbiased whole-brain mapping of food odour-induced brain activity revealed a potent activation of the medial septum (MS), where food odours selectively activate MS glutamatergic neurons (MSVGLUT2). Activity dynamics of MSVGLUT2 neurons uncovered a biphasic modulation of their neuronal activity with a transient activation after detection of food odours and a long-lasting inhibition following food ingestion, independent of the caloric value and identity of the food. MSVGLUT2 neurons receive direct projections from the olfactory bulb (OB) and acute optogenetic stimulation of OB→MS projections selectively before food ingestion decreased feeding in lean mice. However, acute OB→MS optogenetic stimulation in diet-induced obese mice failed to reduce feeding, suggesting the involvement of this pathway in calorie-rich diet-induced hyperphagia and obesity development. Altogether, our study uncovered a sensory circuit by which the organism integrates olfactory food cues to prime satiety at the outset of a meal. The authors describe a sensory circuit involving the medial septum (MS), where MS glutamatergic neurons integrate food odours to prime satiety and regulate nutrient intake.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"7 6","pages":"1246-1265"},"PeriodicalIF":20.8,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s42255-025-01301-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144260243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GLP-1-mediated synaptic plasticity in feeding regulation is modulated by energy state","authors":"","doi":"10.1038/s42255-025-01304-y","DOIUrl":"10.1038/s42255-025-01304-y","url":null,"abstract":"Glucagon-like peptide 1 (GLP-1) receptor-expressing neurons in the paraventricular nucleus of the hypothalamus send descending excitatory projections to the dorsal vagal complex of the brainstem. GLP-1 signalling regulates synaptic transmission in this circuit in an energy state-dependent manner to control feeding and energy homeostasis.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"7 7","pages":"1318-1319"},"PeriodicalIF":20.8,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144252762","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}

{"title":"State-dependent central synaptic regulation by GLP-1 is essential for energy homeostasis","authors":"Le Wang, Rohan H. Savani, Yi Lu, Matteo Bernabucci, Jorge Luis-Islas, Erin Park, Ishnoor Singh, Wei Xu, Abdelfattah El Ouaamari, Michael B. Wheeler, Harvey J. Grill, Mark A. Rossi, Zhiping P. Pang","doi":"10.1038/s42255-025-01305-x","DOIUrl":"10.1038/s42255-025-01305-x","url":null,"abstract":"Central glucagon-like peptide-1 (GLP-1), secreted by a distinct population of nucleus tractus solitarius neurons, suppresses feeding but the exact mechanisms of action in the brain remain unclear. Here, we investigate a descending circuit formed by GLP-1 receptor (GLP-1R) neurons in the paraventricular hypothalamic nucleus (PVNGLP-1R) projecting to the dorsal vagal complex (DVC) of the brain stem in mice. PVNGLP-1R→DVC synapses release glutamate and are augmented by GLP-1. Chemogenetic activation of PVNGLP-1R→DVC suppresses feeding. Under an energy deficit (that is, hunger) state, synaptic strength is weaker but is more profoundly augmented by GLP-1R activation than under energy-replete state. In an obese condition, the dynamic synaptic changes in this circuit are disrupted. Optogenetic activation of PVNGLP-1R→DVC projections suppresses food intake energy state dependently, and blocking its synaptic release or ablating GLP-1Rs in the presynaptic neurons impairs metabolic health. These findings indicate that the state-dependent synaptic regulation by GLP-1 in PVNGLP-1R→DVC descending circuit is important for energy homeostasis. In this paper, the authors describe the energy state-dependent regulation of the PVNGLP-1R to DVC circuit, resulting in altered food intake and metabolic health, mediated by GLP-1 receptor signalling.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"7 7","pages":"1443-1458"},"PeriodicalIF":20.8,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144211207","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}

{"title":"Cysteine depletion triggers adipose tissue thermogenesis and weight loss","authors":"Aileen H. Lee, Lucie Orliaguet, Yun-Hee Youm, Rae Maeda, Tamara Dlugos, Yuanjiu Lei, Daniel Coman, Irina Shchukina, Prabhakar Sairam Andhey, Steven R. Smith, Eric Ravussin, Krisztian Stadler, Bandy Chen, Maxim N. Artyomov, Fahmeed Hyder, Tamas L. Horvath, Marc Schneeberger, Yuki Sugiura, Vishwa Deep Dixit","doi":"10.1038/s42255-025-01297-8","DOIUrl":"10.1038/s42255-025-01297-8","url":null,"abstract":"Caloric restriction and methionine restriction-driven enhanced lifespan and healthspan induces ‘browning’ of white adipose tissue, a metabolic response that increases heat production to defend core body temperature. However, how specific dietary amino acids control adipose thermogenesis is unknown. Here, we identified that weight loss induced by caloric restriction in humans reduces thiol-containing sulfur amino acid cysteine in white adipose tissue. Systemic cysteine depletion in mice causes lethal weight loss with increased fat utilization and browning of adipocytes that is rescued upon restoration of cysteine in diet. Mechanistically, cysteine-restriction-induced adipose browning and weight loss requires sympathetic nervous system-derived noradrenaline signalling via β3-adrenergic-receptors that is independent of FGF21 and UCP1. In obese mice, cysteine deprivation induced rapid adipose browning, increased energy expenditure leading to 30% weight loss and reversed metabolic inflammation. These findings establish that cysteine is essential for organismal metabolism as removal of cysteine in the host triggers adipose browning and rapid weight loss. The authors describe how reduced dietary availability and systemic loss of cysteine leads to adipose tissue browning and rapid weight loss in mice and humans.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"7 6","pages":"1204-1222"},"PeriodicalIF":20.8,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s42255-025-01297-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144201900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"β-hydroxybutyrate inhibits Plasmodium falciparum development and confers protection against malaria in mice","authors":"Zhiming Wei, Ning Jiang, Yiwei Zhang, Qilong Li, Ziwei Su, Yanxin Zhang, Kunying Lv, Yixin Yang, Tong Liu, Lu Sun, Kexin Zheng, Ang Li, Anni Feng, Xiaoyu Sang, Ying Feng, Ran Chen, Qijun Chen","doi":"10.1038/s42255-025-01302-0","DOIUrl":"10.1038/s42255-025-01302-0","url":null,"abstract":"Environmental factors restrict malaria parasite development, but the influence of host metabolic variations on the infectivity of the blood stage parasite is not fully understood. Here we show that mice on a ketogenic diet are completely protected from infection with the malaria parasite Plasmodium berghei. We further show that administration of the ketone body β-hydroxybutyrate (βOHB), but not of acetoacetate, increases survival of infected mice and inhibits proliferation of both P. berghei and Plasmodium falciparum in vitro. Administration of either a ketogenic diet or βOHB induces metabolic reprogramming in parasites, including reduced levels of nicotinamide adenine dinucleotide, which is associated with the downregulation of genes controlling parasite development, erythrocyte invasion and pathogenicity. Our data indicate that a ketogenic diet and the ketone body βOHB confer resistance to malaria in mice by causing developmental arrest of Plasmodium parasites, highlighting the potential of dietary and metabolic strategies to fight malarial infection. A ketogenic diet and the ketone body β-hydroxybutyrate are shown to confer resistance to malaria in mice by inducing metabolic reprogramming in Plasmodium parasites, suggesting a dietary strategy for malaria prevention.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"7 7","pages":"1330-1343"},"PeriodicalIF":20.8,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s42255-025-01302-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144122945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A ketogenic diet halts malaria parasite growth","authors":"Temitope W. Ademolue, Lena Pernas","doi":"10.1038/s42255-025-01310-0","DOIUrl":"10.1038/s42255-025-01310-0","url":null,"abstract":"A new study reveals that the host-derived ketone body, β-hydroxybutyrate, protects against malaria in mice by inhibiting Plasmodium development. These findings highlight the anti-microbial potential of metabolic interventions.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"7 7","pages":"1305-1306"},"PeriodicalIF":20.8,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144122944","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}