Physiology

NK2R signaling governs intestinal lipid mobilization and mucosal inflammation

1. Pedro A. Perez
2. Chung-Chih Liu
3. Alessandra Ferrari
4. Nicole Littlejohn
5. John Paul Kennelly
6. Emma Robinson
7. Vân T B Nguyen-Tran
8. Jon Athanacio
9. Sean B Joseph
10. Zaid Amso
11. Peter Tontonoz
12. Supriya Srinivasan

• Curated by eLife

  eLife Assessment

  This is an important study on the role of the neurokinin-2 receptor (NK2R) as a regulatory node connecting intestinal lipid metabolism, mucosal immunity, and the gut microbiome, bidirectionally regulating enterocyte lipid uptake, lipid droplet storage, chylomicron output, and systemic metabolic parameters in DIO mice. The authors present solid evidence linking Tacr2 deletion to reprogrammed epithelial lineage allocation, dampened immune gene expression, and male-biased protection from DSS colitis, despite dysbiotic microbiota. However, the causal evidence for some mechanistic and pro-inflammatory NK2R claims remains incomplete and potentially confounding, requiring additional cell-type-specific and functional experiments.

Reviewed by eLife

Differential Regulation of Hepatic Macrophage Fate by Chi3l1 in MASLD

1. Jia He
2. Bo Chen
3. Weiju Lu
4. Xiong Wang
5. Ruoxue Yang
6. Chengxiang Deng
7. Xiane Zhu
8. Keqin Wang
9. Lang Wang
10. Cheng Xie
11. Rui Li
12. Xiaokang Lu
13. Ruizhi Yang
14. Cheng Peng
15. Canpeng Li
16. Zhao Shan

• Curated by eLife

  eLife Assessment

  This study provides an insight into the role of a Chi3l1 in liver macrophages during metabolic disease. The evidence is solid with the authors now addressing most concerns, although one key conclusion is not fully supported by the data presented. Overall, the work offers a useful contribution to the field.

Reviewed by eLife

Cytokine control of systemic hypoxia tolerance in Drosophila

1. Kate Ding
2. Prajakta Bodkhe
3. Byoungchun Lee
4. Danielle Polan
5. Amy Wycislik
6. Tiffany Cheung
7. Sophie Wu
8. Savraj S Grewal

Reviewed by Review Commons, PREreview

Zinc is a Key Regulator of the Sperm-Specific K+ Channel (Slo3) Function

1. Rizki Tsari Andriani
2. Tanadet Pipatpolkai
3. Haruhiko Miyata
4. Masahito Ikawa
5. Yasushi Okamura
6. Takafumi Kawai

• Curated by eLife

  eLife Assessment

  This study presents a valuable finding on the role of intracellular zinc as a regulator of the sperm-specific potassium channel Slo3, demonstrating that zinc export during capacitation contributes to alkalinization-induced membrane hyperpolarization. The electrophysiological evidence supporting zinc-mediated inhibition of Slo3 is solid, though the mechanistic basis of this inhibition is not complete, as the proposed zinc-binding site involving E169 and E205 has not been directly tested through double-mutant analysis. This work will be of interest to reproductive biologists and ion channel biophysicists studying the molecular mechanisms of sperm capacitation.

Reviewed by eLife

Natural xanthones as α-Mangostin induce vasorelaxation involving key gating residues in the S6 domain of BK channels

1. Soenke Cordeiro
2. Robert Patejdl
3. Thomas Baukrowitz
4. Marianne A Musinszki

• Curated by eLife

  eLife Assessment

  The present manuscript by Cordeiro et al., shows convincing evidence that α-mangostin, a xanthone obtained from the fruit of the Garcinia mangostana tree, behaves as a strong activator of the large-conductance (BK) potassium channels. The authors suggest that α-mangostin activation of the BK channel is state-independent, and molecular docking and mutagenesis suggest that α-mangostin binds to a site in the internal cavity. Additionally, the authors show that α-mangostin can relax arteries, further suggesting the plausibility of the proposed effects of this compound. These are valuable findings that should be of interest to channel biophysicists and physiologists alike.

Reviewed by eLife

Metabolism fine tuning and cardiokines secretion represent adaptative responses of the heart to High Fat and High Sugar Diets in flies

1. Lucie Khamvongsa-Charbonnier
2. Laurent Kremmer
3. Magali Torres
4. Sallouha Krifa
5. Charis Aubert
6. Alice Corbet
7. Loïc Crespo
8. Laurence Röder
9. Laurent Perrin
10. Nathalie Arquier

Reviewed by Review Commons

The Hypothalamic–Pituitary–Adrenal Axis Orchestrates Energy Homeostasis during Cold Exposure

1. Mireia Llerins Perez
2. Xinran Gao
3. Laura Heimerl
4. Yuanyuan Wang
5. Katharina Schnabl
6. Uwe Firzlaff
7. Harald Luksch
8. Martin Klingenspor
9. Nina Henriette Uhlenhaut
10. Dehua Wang
11. Yongguo Li

Reviewed by PREreview

Single transcript level atlas of oxytocin and the oxytocin receptor in the mouse brain

1. Vitaly Ryu
2. Anisa Azatovna Gumerova
3. Georgii Pevnev
4. Funda Korkmaz
5. Hasni Kannangara
6. Liam Cullen
7. Farhath Sultana
8. Ronit Witztum
9. Steven Lee Sims
10. Tal Frolinger
11. Ofer Moldavski
12. Orly Barak
13. Emily Weiss
14. Jay J Cao
15. Daria Lizneva
16. Ki A Goosens
17. Tony Yuen
18. Mone Zaidi

• Curated by eLife

  eLife Assessment

  This fundamental work substantially advances our understanding of OXT (oxytocin) neurons and OXTR (oxytocin receptor) expressions in mammalian brains using an advanced RNAscope at the single transcript level. The evidence supporting the conclusions is compelling using chromogenic assays and state-of-the-art microscopy. The work will be of broad interest to neuroscientists and endocrinologists.

Reviewed by eLife

RiboTRAP-seq identifies spatially distinct functions for the anterior and posterior intestine in immune and metabolic regulation in C. elegans

1. Chung-Chih Liu
2. Nicolas Seban
3. Supriya Srinivasan

• Curated by eLife

  eLife Assessment

  In this valuable study, the authors performed cell-specific ribosome pulldown to identify gene expression (translatome) differences in the anterior (NT1) vs middle & posterior (NT2-9) cells of the C. elegans intestine, under fed, starved, or refeeding conditions. The data generated will be very helpful to the C. elegans community, and the evidence supporting the conclusions of the study is assessed to be solid. Some methodological caveats remain and are discussed.

Reviewed by eLife

Efficient transduction of pancreas tissue slices with genetically encoded calcium integrators

1. Charles S Lazimi
2. Austin E Stis
3. Julia K Panzer
4. Helmut Hiller
5. Maria L Beery
6. Amelia K Linnemann
7. Cherie L Stabler
8. Clayton E Mathews
9. Edward A Phelps

• Curated by eLife

  eLife Assessment

  This study presents a valuable advance by enabling functional mapping of Ca²⁺ responses in live human pancreatic tissue slices, providing new opportunities to study islet heterogeneity and diabetes-related dysfunction in an intact tissue context. The evidence supporting the main conclusions is solid, based on reproducible methodology and functional validation across multiple human donor samples. Key revisions needed include clearer quantification of transduction efficiency and tissue viability, and improved clarification of how CaMPARI2 signals should be interpreted.

Reviewed by eLife