bims-nimamd Biomed News
on Neuroimmunity and neuroinflammation in ageing and metabolic disease
Issue of 2026–10–25
nineteen papers selected by
Fawaz Alzaïd, Sorbonne Université
  1. GutPath links immune archetypes and single-cell landscapes in the infected gut.
  2. Type 2 immunity as a counter-regulatory axis in aging.
  3. Distinguishing hepatic metabolic effects from overall cardiometabolic benefit after matched weight loss.
  4. Obesity and Starvation.
  5. Body-clock disruptions contribute to one in four cases of depression, suggests large study.
  6. Putting glucose metabolism under electronic control.
  7. The human microbiome and chronic disease: ten strategic priorities for research and public health.
  8. Response to Magkos and Silva: Diet macronutrient content and metabolic function in metabolically unhealthy obesity.
  9. Teen depression and anxiety predicted by childhood brain development.
  10. WHO Publishes First Guidelines for Managing Obesity in Children.
  11. On the interpretation of diet-specific metabolic effects following weight loss.
  12. Wireless electrocatalytic closed-loop system for drug-free management of diabesity.
  13. Attractin-like protein 1 is an essential partner of MC4R to regulate body weight.
  14. Steatotic Liver Disease Is Becoming a Higher Priority Worldwide.
  15. Genome-wide analyses identify 60 loci associated with liver triglyceride content.
  16. Monocyte surface Y RNAs potentiate innate immunity.
  17. A single-cell atlas of human neutrophils reveals neutrophil heterogeneity across health and disease.
  18. Metabolic hallmarks of regulated cell death.
  19. METTL14-mediated m6A methylation orchestrates early NK cell development by maintaining metabolic fitness.
  1. Nat Immunol. 2026 Oct 23.
    GutPath links immune archetypes and single-cell landscapes in the infected gut.
      
    DOI:  https://doi.org/10.1038/s41590-026-02719-9
  2. Nat Aging. 2026 Oct 23.
    Type 2 immunity as a counter-regulatory axis in aging.
    Jingfei Yao, Yifu Qiu, Yi Zhang.
      
    DOI:  https://doi.org/10.1038/s43587-026-01265-1
  3. Cell Metab. 2026 Oct 22. pii: S1550-4131(26)00389-X. [Epub ahead of print]
    Distinguishing hepatic metabolic effects from overall cardiometabolic benefit after matched weight loss.
    André Marques Fernandes Silva.
      
    DOI:  https://doi.org/10.1016/j.cmet.2026.09.014
  4. JAMA. 2026 Oct 22.
    Obesity and Starvation.
      
    DOI:  https://doi.org/10.1001/jama.2025.16106
  5. Nature. 2026 Oct 20.
    Body-clock disruptions contribute to one in four cases of depression, suggests large study.
    Rachel Fieldhouse.
      
    Keywords:  Depression; Medical research; Psychiatric disorders
    DOI:  https://doi.org/10.1038/d41586-026-03359-7
  6. Science. 2026 Oct 22. 394(6822): 382-383
    Putting glucose metabolism under electronic control.
    W E Bentley, G F Payne.
      An electronic device controls the redox mechanisms that regulate glucose concentrations in mice.
    DOI:  https://doi.org/10.1126/science.aem0762
  7. Nat Med. 2026 Oct 23.
    The human microbiome and chronic disease: ten strategic priorities for research and public health.
    Martin J Blaser, Frederic D Bushman, Maria Gloria Dominguez-Bello, Eran Elinav, Sangeeta Khare, Rob Knight, Jennie H Kwon, Sarkis K Mazmanian, Majdi Osman, Nicola Segata, Tim Spector, Jennifer A Wargo, Suchitra K Hourigan.
      
    DOI:  https://doi.org/10.1038/s41591-026-04730-x
  8. Cell Metab. 2026 Oct 22. pii: S1550-4131(26)00386-4. [Epub ahead of print]
    Response to Magkos and Silva: Diet macronutrient content and metabolic function in metabolically unhealthy obesity.
    Max C Petersen, Gordon I Smith, Samuel Klein.
      
    DOI:  https://doi.org/10.1016/j.cmet.2026.09.011
  9. Nature. 2026 Oct 22.
    Teen depression and anxiety predicted by childhood brain development.
    Max Kozlov.
      
    Keywords:  Brain; Developmental biology
    DOI:  https://doi.org/10.1038/d41586-026-03357-9
  10. JAMA. 2026 Oct 23.
    WHO Publishes First Guidelines for Managing Obesity in Children.
    Samantha Anderer.
      
    DOI:  https://doi.org/10.1001/jama.2026.20033
  11. Cell Metab. 2026 Oct 22. pii: S1550-4131(26)00385-2. [Epub ahead of print]
    On the interpretation of diet-specific metabolic effects following weight loss.
    Faidon Magkos.
      
    DOI:  https://doi.org/10.1016/j.cmet.2026.09.010
  12. Science. 2026 Oct 22. 394(6822): eady8560
    Wireless electrocatalytic closed-loop system for drug-free management of diabesity.
    Debasis Maity, Preetam Guha Ray, Peter Buchmann, Ghislaine Charpin-El Hamri, Martin Fussenegger.
      Lifestyle-related type 2 diabetes and associated obesity (diabesity) affect >2.5 billion people worldwide and impose nearly $3 trillion in annual health care costs. We developed an implantable, wirelessly powered electrocatalytic closed-loop health optimization (ECHO) device containing platinum-decorated gold nanoclusters embedded in graphite felt that enabled selective, electrically tunable oxidation of blood glucose to renally cleared gluconate. In type 2 diabetic mice, wireless, low-power activation (0.75 volts, 10 milliamperes) restored glucose homeostasis within 1 hour, shifted metabolism from glucose to lipid utilization, reduced body weight and triglycerides, and increased circulating free fatty acids and ketone bodies without detectable hypoglycemia or adverse physiological, inflammatory, or behavioral effects during 6 weeks of treatment. Coupling this ECHO device to a commercial continuous glucose monitoring system enabled autonomous, smartphone-controlled, drug-free closed-loop management of experimental diabesity.
    DOI:  https://doi.org/10.1126/science.ady8560
  13. Nat Commun. 2026 Sep 22. pii: 11041. [Epub ahead of print]17(1):
    Attractin-like protein 1 is an essential partner of MC4R to regulate body weight.
    Paul Buscaglia, Kate R Bowman, Katherine Lawler, Ciria C Hernandez, Jacopo Scotucci, Rebecca Bounds, Julia M Keogh, Elana Henning, Roger D Cone, I Sadaf Farooqi, Julien A Sebag.
      The melanocortin 4 receptor (MC4R) plays a critical role in the central control of energy homeostasis, and its disruption causes severe early-onset obesity. MC4R signaling is tightly regulated by endogenous agonists and antagonists, as well as the accessory protein MRAP2. The single transmembrane protein attractin-like protein 1 (ATRNL1) is a known interactor of MC4R, however, its effect on MC4R signaling and physiological function is not well understood. Here we show that ATRNL1 interacts with MC4R to amplify its signaling in cells and that expression of ATRNL1 potentiates agonist-induced activation of MC4R neurons. Deletion of Atrnl1 in MC4R neurons increased food intake and body weight in rodents. In exomes from 1,623 children with severe early-onset obesity, we identified multiple rare ATRNL1 variants that impair ATRNL1-mediated regulation of MC4R signaling. Cumulatively, these findings establish ATRNL1 as an important regulator of mammalian energy homeostasis.
    DOI:  https://doi.org/10.1038/s41467-026-77897-z
  14. JAMA. 2026 Oct 23.
    Steatotic Liver Disease Is Becoming a Higher Priority Worldwide.
    Rita Rubin.
      
    DOI:  https://doi.org/10.1001/jama.2026.18418
  15. Nat Genet. 2026 Oct 21.
    Genome-wide analyses identify 60 loci associated with liver triglyceride content.
    Oveis Jamialahmadi, Shahir Mowlaei, Kyla Z Gelev, Rosellina M Mancina, Valentina Flagiello, Julia Kozlitina, Päivi Pajukanta, Luca Valenti, Stefano Romeo.
      We performed a large-scale genome-wide association study meta-analysis of magnetic resonance imaging-derived liver triglyceride content across 71,488 European-ancestry participants from the UK Biobank, approximately doubling the sample size of previous genome-wide association studies1. We identified 60 independent loci, including 31 not previously reported, and estimated the single nucleotide polymorphism-based heritability of liver triglyceride content at 25%. Integrative fine-mapping and gene-prioritization analyses nominated candidate effector genes for 48 loci. Of the 31 newly identified variants, 14 were validated in meta-analyses of clinically diagnosed metabolic dysfunction-associated steatotic liver disease (42,163 cases and 1,646,254 controls). People in the highest versus lowest decile of a polygenic risk score for liver triglyceride content had 2.71-fold higher odds of cirrhosis and 7.47-fold higher odds of hepatocellular carcinoma. Plasma proteins associated with the liver triglyceride polygenic risk score were enriched for metabolic remodeling and inflammatory pathways, with liver-enriched protein signatures increasing and visceral adipose signatures decreasing with higher genetic risk. Together, these findings refine the genetic architecture of liver triglyceride content, linking polygenic susceptibility to downstream metabolic and inflammatory pathways and providing insights into the genetic basis of steatotic liver disease.
    DOI:  https://doi.org/10.1038/s41588-026-02794-6
  16. Nat Cell Biol. 2026 Oct 19.
    Monocyte surface Y RNAs potentiate innate immunity.
    Xiao Jiang, Weizhi He, Chu Xu, Wanwei Zheng, Chenye Li, Danhua Xu, Qixin Shao, Yin Li, Zhuo Liu, Wenshuai Li, Shuang He, Zhiqiang Wang, Ronghua Liu, Yiwei Chu, Zhongguang Luo, Xinxin Huang, Jie Liu, Enzhuo Yang, Lulu Hu.
      RNAs can associate with the surface of diverse cell types, yet the functions of specific RNA species on primary immune cells remain unclear. Here, utilizing methods developed to profile, image and quantify surface RNAs in rare primary cell populations, we found that Y RNAs, a family of small noncoding RNAs, preferentially localize to human monocyte surface. In an exploratory pooled inflammatory bowel disease cohort, the proportion of cell-surface-Y-RNA-positive peripheral monocytes was markedly higher in patients with inflammatory bowel disease than in healthy donors or individuals with irritable bowel syndrome. In vivo depletion of cell-surface Y RNAs ameliorates disease activity in mice with colitis. Mechanistically, cell-surface Y RNAs co-cluster with Toll-like receptors TLR2 and TLR4, bind extracellular histones and promote receptor-mediated histone recognition, thereby activating NF-κB and AP-1 signalling and increasing IL6 expression and IL-6 secretion. These findings identify cell-surface Y RNAs as previously unrecognized amplifiers of inflammatory activation.
    DOI:  https://doi.org/10.1038/s41556-026-02100-w
  17. Nat Immunol. 2026 Oct 21.
    A single-cell atlas of human neutrophils reveals neutrophil heterogeneity across health and disease.
    Hong Zheng, Evan Maestri, Andrew R Moore, Ananthakrishnan Ganesan, Jeanna Enriquez, Verónica Durán, Shirit Einav, Tom van der Poll, Hjalmar R Bouma, Mihir R Atreya, Philip A Efron, Lyle L Moldawer, Jonathan Sevransky, David W Wright, Ignacio Martin-Loeches, Thomas Karvunidis, Jeremiah Hinson, David N Hager, Richard E Rothman, Evangelos J Giamarellos-Bourboulis, Timothy E Sweeney, Angela J Rogers, Saurabh Gombar, Manoj V Maddali, Jonathan H Chen, Nigam Shah, Purvesh Khatri.
      Neutrophils, the most abundant leukocytes in human blood, have multifaceted roles in health and disease. Here we assembled a single-cell atlas of human neutrophils (SCAHN) by integrating transcriptome data from 1 million human neutrophils from 781 samples and 43 independent datasets. Using SCAHN, we identified multiple neutrophil subsets with distinct functions across tissues and robust changes in gene expression and subset proportions in infection, cancer, immune suppression and sex differences at single-cell resolution. Cross-species reference mapping of mouse and nonhuman primate neutrophils onto SCAHN revealed both conserved and species-specific features. Using 17,023 bulk blood transcriptome profiles from 40 datasets, we found that neutrophil-specific signatures predicted mortality in acutely ill patients at presentation, were associated with cancer diagnosis and survival, and correlated with metabolic dysfunction and long-term all-cause mortality. Our study highlights how neutrophil biology can improve immune risk stratification and develop effective diagnostic and therapeutic strategies.
    DOI:  https://doi.org/10.1038/s41590-026-02671-8
  18. Cell Res. 2026 Oct 20.
    Metabolic hallmarks of regulated cell death.
    Rui Kang, Xin Chen, Guido Kroemer, Daolin Tang.
      Regulated cell death (RCD) is characterized by distinct molecular execution mechanisms, but its initiation, progression, and biological consequences are increasingly recognized as being shaped by cellular metabolism. Bioenergetic state, redox homeostasis, nutrient availability, metal ion metabolism, inflammatory metabolism, and organelle function collectively determine cellular susceptibility to death and influence the activation and execution of diverse RCD programs. In this review, we synthesize the metabolic hallmarks of established, independently validated, and recently proposed forms of RCD, highlighting both their mechanistic diversity and their extensive metabolic convergence. We then examine the endogenous mechanisms that maintain metabolic homeostasis and discuss how their disruption reshapes cell death responses in human disease and therapeutic contexts. Together, these insights provide a guide to  the metabolic landscape of RCD and reveal metabolism not only as a modifier of cell death, but as a fundamental determinant of when, how, and with what consequences cells die. We conclude by discussing key conceptual and mechanistic challenges and emerging opportunities for therapeutically exploiting the metabolic control of RCD.
    DOI:  https://doi.org/10.1038/s41422-026-01306-9
  19. Cell Death Dis. 2026 Jul 28. pii: 905. [Epub ahead of print]17(1):
    METTL14-mediated m6A methylation orchestrates early NK cell development by maintaining metabolic fitness.
    Huan Ma, Zhenzhen Tu, Surong Deng, Yirong Sun, Shuxin Wang, Hongxia Wang, Chen Cheng, Xiang Li, Zhongjun Dong, Shasha Chen.
      N6-methyladenosine (m6A) represents the most abundant mRNA modification, yet its role in natural killer (NK) cell development remains incompletely understood. Here we demonstrate that the m6A methyltransferase METTL14 plays an indispensable, stage-specific role in early NK cell development. Mettl14 deficiency at the progenitor stage caused severe NK cell lymphopenia by disrupting the NK progenitor to immature NK cell transition. Paradoxically, residual Mettl14-null NK cells exhibited a hypermetabolic state characterized by mTORC1 hyperactivation and enhanced mitochondrial function, which drove both hyperproliferation and activation-induced cell death via p53 and apoptotic pathway activation. Despite developmental defects, these cells demonstrated superior capacity to control melanoma metastasis in vivo. Mechanistically, METTL14 fine-tuned IL-15 responsiveness likely by sustaining SOCS3 expression to restrain JAK-STAT5 signaling. Terminal deletion of Mettl14 produced no phenotype, underscoring its specific requirement during early development. Our findings establish METTL14 as a crucial checkpoint coordinating transcriptional and metabolic programs to ensure NK cell homeostasis.
    DOI:  https://doi.org/10.1038/s41419-026-09069-2
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