Nature metabolism最新文献

Non-caloric sweetener effects on brain appetite regulation in individuals across varying body weights

IF 18.9 1区医学

Nature metabolism Pub Date : 2025-03-26 DOI: 10.1038/s42255-025-01227-8

Sandhya P. Chakravartti, Kay Jann, Ralf Veit, Hanyang Liu, Alexandra G. Yunker, Brendan Angelo, John R. Monterosso, Anny H. Xiang, Stephanie Kullmann, Kathleen A. Page

{"title":"Non-caloric sweetener effects on brain appetite regulation in individuals across varying body weights","authors":"Sandhya P. Chakravartti, Kay Jann, Ralf Veit, Hanyang Liu, Alexandra G. Yunker, Brendan Angelo, John R. Monterosso, Anny H. Xiang, Stephanie Kullmann, Kathleen A. Page","doi":"10.1038/s42255-025-01227-8","DOIUrl":"10.1038/s42255-025-01227-8","url":null,"abstract":"Sucralose, a widely used non-caloric sweetener, provides sweet taste without calories. Some studies suggest that non-caloric sweeteners stimulate appetite, possibly owing to the delivery of a sweet taste without the post-ingestive metabolic signals that normally communicate with the hypothalamus to suppress hunger. In a randomized crossover trial (ClinicalTrials.gov identifier: NCT02945475 ), 75 young adults (healthy weight, overweight or with obesity) consumed a drink containing sucralose, sweetness-matched sucrose or water. We show that acute consumption of sucralose versus sucrose stimulates hypothalamic blood flow (P < 0.018) and greater hunger responses (P < 0.001). Sucralose versus water also increases hypothalamic blood flow (P < 0.019) but produces no difference in hunger ratings. Sucrose, but not sucralose, increases peripheral glucose levels, which are associated with reductions in medial hypothalamic blood flow (P < 0.007). Sucralose, compared to sucrose and water, results in increased functional connections between the hypothalamus and brain regions involved in motivation and somatosensory processing. These findings suggest that non-caloric sweeteners could affect key mechanisms in the hypothalamus responsible for appetite regulation. In a randomized, crossover clinical trial in healthy young adults with varying weights, sucralose increased hypothalamic blood flow and its functional connections with brain regions involved in motivation and somatosensory processing.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"7 3","pages":"574-585"},"PeriodicalIF":18.9,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707711","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}

引用次数: 0

Haem biosynthesis regulates BCAA catabolism and thermogenesis in brown adipose tissue

IF 20.8 1区医学

Nature metabolism Pub Date : 2025-03-25 DOI: 10.1038/s42255-025-01253-6

Dylan J. Duerre, Julia K. Hansen, Steven V. John, Annie Jen, Noah D. Carrillo, Hoang Bui, Yutong Bao, Matias Fabregat, J. Leon Catrow, Li-Yu Chen, Katherine A. Overmyer, Evgenia Shishkova, Quentinn Pearce, Mark P. Keller, Richard A. Anderson, Vincent L. Cryns, Alan D. Attie, James E. Cox, Joshua J. Coon, Jing Fan, Andrea Galmozzi

{"title":"Haem biosynthesis regulates BCAA catabolism and thermogenesis in brown adipose tissue","authors":"Dylan J. Duerre, Julia K. Hansen, Steven V. John, Annie Jen, Noah D. Carrillo, Hoang Bui, Yutong Bao, Matias Fabregat, J. Leon Catrow, Li-Yu Chen, Katherine A. Overmyer, Evgenia Shishkova, Quentinn Pearce, Mark P. Keller, Richard A. Anderson, Vincent L. Cryns, Alan D. Attie, James E. Cox, Joshua J. Coon, Jing Fan, Andrea Galmozzi","doi":"10.1038/s42255-025-01253-6","DOIUrl":"https://doi.org/10.1038/s42255-025-01253-6","url":null,"abstract":"The distinctive colour of brown adipose tissue (BAT) is attributed to its high content of haem-rich mitochondria. However, the mechanisms by which BAT regulates intracellular haem levels remain largely unexplored. Here we demonstrate that haem biosynthesis is the primary source of haem in brown adipocytes. Inhibiting haem biosynthesis results in an accumulation of the branched-chain amino acids (BCAAs) valine and isoleucine, owing to a haem-associated metabolon that channels BCAA-derived carbons into haem biosynthesis. Haem synthesis-deficient brown adipocytes display reduced mitochondrial respiration and lower UCP1 levels than wild-type cells. Although exogenous haem supplementation can restore intracellular haem levels and mitochondrial function, UCP1 downregulation persists. This sustained UCP1 suppression is linked to epigenetic regulation induced by the accumulation of propionyl-CoA, a byproduct of disrupted haem synthesis. Finally, disruption of haem biosynthesis in BAT impairs thermogenic response and, in female but not male mice, hinders the cold-induced clearance of circulating BCAAs in a sex-hormone-dependent manner. These findings establish adipose haem biosynthesis as a key regulator of thermogenesis and sex-dependent BCAA homeostasis.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"61 1","pages":""},"PeriodicalIF":20.8,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143695623","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}

引用次数: 0

A BCAA–haem axis regulates brown fat function

IF 20.8 1区医学

Nature metabolism Pub Date : 2025-03-25 DOI: 10.1038/s42255-025-01266-1

引用次数: 0

Reversible reduction in brain myelin content upon marathon running

IF 20.8 1区医学

Nature metabolism Pub Date : 2025-03-24 DOI: 10.1038/s42255-025-01244-7

Pedro Ramos-Cabrer, Alberto Cabrera-Zubizarreta, Daniel Padro, Mario Matute-González, Alfredo Rodríguez-Antigüedad, Carlos Matute

引用次数: 0

Reversible reduction in brain myelin content after endurance exercise

IF 20.8 1区医学

Nature metabolism Pub Date : 2025-03-24 DOI: 10.1038/s42255-025-01251-8

引用次数: 0

Author Correction: Metagenomic estimation of dietary intake from human stool 作者更正：从人类粪便的元基因组估算膳食摄入量。

IF 18.9 1区医学

Nature metabolism Pub Date : 2025-03-24 DOI: 10.1038/s42255-025-01284-z

Christian Diener, Hannah D. Holscher, Klara Filek, Karen D. Corbin, Christine Moissl-Eichinger, Sean M. Gibbons

引用次数: 0

Vestibular nucleus mediation of motion sickness has implications for obesity control

IF 20.8 1区医学

Nature metabolism Pub Date : 2025-03-21 DOI: 10.1038/s42255-025-01238-5

引用次数: 0

Vestibular neurons link motion sickness, behavioural thermoregulation and metabolic balance in mice

IF 20.8 1区医学

Nature metabolism Pub Date : 2025-03-21 DOI: 10.1038/s42255-025-01234-9

Longlong Tu, Xing Fang, Yongjie Yang, Meng Yu, Hailan Liu, Hesong Liu, Na Yin, Jonathan C. Bean, Kristine M. Conde, Mengjie Wang, Yongxiang Li, Olivia Z. Ginnard, Qingzhuo Liu, Yuhan Shi, Junying Han, Yi Zhu, Makoto Fukuda, Qingchun Tong, Benjamin Arenkiel, Mingshan Xue, Yang He, Chunmei Wang, Yong Xu

{"title":"Vestibular neurons link motion sickness, behavioural thermoregulation and metabolic balance in mice","authors":"Longlong Tu, Xing Fang, Yongjie Yang, Meng Yu, Hailan Liu, Hesong Liu, Na Yin, Jonathan C. Bean, Kristine M. Conde, Mengjie Wang, Yongxiang Li, Olivia Z. Ginnard, Qingzhuo Liu, Yuhan Shi, Junying Han, Yi Zhu, Makoto Fukuda, Qingchun Tong, Benjamin Arenkiel, Mingshan Xue, Yang He, Chunmei Wang, Yong Xu","doi":"10.1038/s42255-025-01234-9","DOIUrl":"https://doi.org/10.1038/s42255-025-01234-9","url":null,"abstract":"Motion sickness is associated with thermoregulation and metabolic control, but the underlying neural circuitry remains largely unknown. Here we show that neurons in the medial vestibular nuclei parvocellular part (MVePC) mediate the hypothermic responses induced by motion. Reactivation of motion-sensitive MVePC neurons recapitulates motion sickness in mice. We show that motion-activated neurons in the MVePC are glutamatergic (MVePCGlu), and that optogenetic stimulation of MVePCGlu neurons mimics motion-induced hypothermia by signalling to the lateral parabrachial nucleus (LPBN). Acute inhibition of MVePC-LPBN circuitry abrogates motion-induced hypothermia. Finally, we show that chronic inhibition of MVePCGlu neurons prevents diet-induced obesity and improves glucose homeostasis without suppressing food intake. Overall, these findings highlight MVePCGlu neurons as a potential target for motion-sickness treatment and obesity control.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"24 1","pages":""},"PeriodicalIF":20.8,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143665917","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}

引用次数: 0

GLP-2 attenuates antipsychotics’ adverse metabolic effects

IF 20.8 1区医学

Nature metabolism Pub Date : 2025-03-20 DOI: 10.1038/s42255-025-01248-3

Sandra Pereira, Margaret K. Hahn

引用次数: 0

GLP-2 prevents antipsychotics-induced metabolic dysfunction in mice

IF 20.8 1区医学

Nature metabolism Pub Date : 2025-03-20 DOI: 10.1038/s42255-025-01252-7

Yanmin Peng, Chenzhang Feng, Shiyu Peng, Ying Wang, Qian Zhang, Zhuolei Jiao, Huateng Cao, Shajin Huang, Peihuang Tian, Xiujia Sun, Xiaohong Xu, Yu Fu, Ji Hu, Zhe Zhang

{"title":"GLP-2 prevents antipsychotics-induced metabolic dysfunction in mice","authors":"Yanmin Peng, Chenzhang Feng, Shiyu Peng, Ying Wang, Qian Zhang, Zhuolei Jiao, Huateng Cao, Shajin Huang, Peihuang Tian, Xiujia Sun, Xiaohong Xu, Yu Fu, Ji Hu, Zhe Zhang","doi":"10.1038/s42255-025-01252-7","DOIUrl":"https://doi.org/10.1038/s42255-025-01252-7","url":null,"abstract":"Antipsychotic drugs have severe metabolic side effects. Acute use can induce hypothermia, while chronic use often leads to weight gain and associated disorders. However, no treatment is currently available for drug-induced hypothermia, and weight control measures lack evidence for long-term effectiveness. Here we demonstrate that a glucagon-like peptide 2 analogue, teduglutide, effectively prevents olanzapine-induced hypothermia and weight gain, and restores glucose tolerance and insulin sensitivity in mice. Mechanistically, olanzapine suppresses prodynorphin-expressing neurons in the ventromedial hypothalamus (VMHPdyn neurons) via serotonin receptor 2C, while teduglutide activates the same neuron population. Selective ablation of VMHPdyn neurons mimics olanzapine-induced side effects. More importantly, chemogenetic activation of VMHPdyn neurons abolishes olanzapine-induced hypothermia and excessive weight gain, although the psychotropic effects remain intact. Together, our data show that VMHPdyn neurons are the crucial mediator of antipsychotic-induced metabolic dysfunction and glucagon-like peptide 2 receptor agonism may be an effective target to mitigate both acute and chronic side effects.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"8 1","pages":""},"PeriodicalIF":20.8,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143661408","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}

引用次数: 0