Physiology

Peripheral opioid receptor antagonism alleviates fentanyl-induced cardiorespiratory depression and is devoid of aversive behavior

1. Brian C Ruyle
2. Sarah Masud
3. Rohith Kesaraju
4. Mubariz Tahirkheli
5. Juhi Modh
6. Caroline G Roth
7. Sofia Angulo-Lopera
8. Tania Lintz
9. Jessica A Higginbotham
10. Nicolas Massaly
11. Jose A Morón

• Curated by eLife

  eLife Assessment

  This manuscript represents a fundamental contribution demonstrating that fentanyl-induced respiratory depression can be reversed with a peripherally-restricted mu opioid receptor antagonist. The paper reports compelling and rigorous physiological, pharmacokinetic, and behavioral evidence supporting this major claim, and furthers mechanistic understanding of how peripheral opioid receptors contribute to respiratory depression. These findings reshape our understanding of opioid-related effects on respiration and have significant therapeutic implications given that medications currently used to reverse opioid overdose (such as naloxone) produce severe aversive and withdrawal effects via actions within the central nervous system.

Reviewed by eLife

Loss of CTRP10 results in female obesity with preserved metabolic health

1. Fangluo Chen
2. Dylan C Sarver
3. Muzna Saqib
4. Leandro M Velez
5. Susan Aja
6. Marcus M Seldin
7. G William Wong

• Curated by eLife

  eLife Assessment

  This manuscript presents a detailed characterization of male and female wildtype and Ctrp10 knockout mice, and reveals that knockout mice develop female-specific obesity that is largely uncoupled from metabolic dysfunction. The data are convincing, and the work will be an important contribution to understanding how obesity is coupled to metabolic dysfunction, and how this can occur in a sex-specific manner.

Reviewed by eLife

Megakaryocytes assemble a three-dimensional cage of extracellular matrix that controls their maturation and anchoring to the vascular niche

1. Claire Masson
2. Cyril Scandola
3. Jean-Yves Rinckel
4. Fabienne Proamer
5. Emily Janus-Bell
6. Fareeha Batool
7. Naël Osmani
8. Jacky G. Goetz
9. Léa Mallo
10. Nathalie Brouard
11. Catherine Léon
12. Alicia Bornert
13. Renaud Poincloux
14. Olivier Destaing
15. Alma Mansson
16. Hong Qian
17. Maxime Lehmann
18. Anita Eckly

• Curated by eLife

  eLife Assessment

  The authors provide a thorough investigation of the interaction of megakaryocytes (MK) with their associated extracellular matrix (ECM) during maturation; they provide evidence that the existence of a dense cage-like pericellular structure containing laminin γ1 and α4 and collagen IV is key to fixing the perisinusoidal localization of MK and preventing their premature intravasation. Adhesion of MK to this ECM cage is dependent on integrin beta1 and beta3 expressed by MK. This strong and solid conclusion is based on the use of state-of-the art techniques such as the use of primary murine bone marrow MK cultures, mice lacking ECM receptors, namely integrin beta1 and beta3 null mice, as well as high-resolution 2D and 3D imaging. The study provides valuable insight into the role of cell-matrix interactions in MK maturation and provides an interesting model with practical implications for the fields of hemostasis and thrombosis.

Reviewed by preLights, eLife

Adiponectin exerts sex-dependent effects on lipid, amino acid, and glucose metabolism during caloric restriction

1. Yoshiko M Ikushima
2. Kuan-Chan Chen
3. Richard J. Sulston
4. Domenico Mattiucci
5. Eleanor J. Brain
6. Stefanie A Fung Xin Zi
7. Karla J. Suchacki
8. Benjamin J. Thomas
9. Andrea Lovdel
10. Matthew Bennett
11. Hiroshi Kobayashi
12. Phillip D. Whitfield
13. Keiyo Takubo
14. Andrew H. Baker
15. Nicholas M. Morton
16. Robert K. Semple
17. William P. Cawthorn

Reviewed by PREreview

The Kv2.2 channel mediates the inhibition of prostaglandin E2 on glucose-stimulated insulin secretion in pancreatic β-cells

1. Chengfang Pan
2. Ying Liu
3. Liangya Wang
4. Wen-Yong Fan
5. Yunzhi Ni
6. Xuefeng Zhang
7. Di Wu
8. Chenyang Li
9. Jin Li
10. Zhaoyang Li
11. Rui Liu
12. Changlong Hu

• Curated by eLife

  eLife Assessment

  The study presents valuable findings on the molecular mechanisms of glucose-stimulated insulin secretion from pancreatic islets, focusing on the main regulatory elements of the signaling pathway in physiological conditions. While the evidence supporting the conclusions is solid, the study can be strengthened by the use of a beta cell line or knockout mice. The work will be of interest to cell biologists and biochemists working on diabetes.

Reviewed by eLife

Blood pressure variability compromises vascular function in middle-aged mice

1. Perenkita J. Mendiola
2. Philip O’Herron
3. Kun Xie
4. Michael W. Brands
5. Weston Bush
6. Rachel E. Patterson
7. Valeria Di Stefano
8. Jessica A. Filosa

• Curated by eLife

  eLife Assessment

  This is an important study providing convincing evidence that increased blood pressure variability impairs myogenic tone and diminishes baroreceptor reflex. The study also provides evidence that blood pressure variability blunts functional hyperemia and contributes to cognitive decline. The authors use appropriate and validated methodology in line with the current state-of-the-art.

Reviewed by eLife

Neuronal Detection Triggers Systemic Digestive Shutdown in Response to Adverse Food Sources

1. Yating Liu
2. Guojing Tian
3. Ziyi Wang
4. Junkang Zheng
5. Huimin Liu
6. Sucheng Zhu
7. Zhao Shan
8. Bin Qi

• Curated by eLife

  eLife Assessment

  This important study investigates how signals from the nervous system can influence the response to different food sources. To demonstrate the role of specific neuronal and intestinal regulators in sensing food quality and modulating digestion, the authors present evidence through a combination of genetic screening, RNA-seq analysis, and functional studies. While the findings shed light on an adaptive strategy to integrate food perception with physiological responses, the evidence presented varies between convincing and incomplete, and additional experiments are needed to more fully support their central hypothesis.

Reviewed by eLife

Multi-dimensional oscillatory activity of mouse GnRH neurons in vivo

1. Su Young Han
2. Shel-Hwa Yeo
3. Jae-Chang Kim
4. Ziyue Zhou
5. Allan E Herbison

• Curated by eLife

  eLife Assessment

  This valuable study investigates the oscillatory activity of gonadotropin-releasing hormone (GnRH) neurones in mice using GCaMP fiber photometry. It demonstrates three distinct patterns of oscillatory activity that occur in GnRH neurons comprising low-level rapid baseline activity, abrupt short-duration oscillations that drive pulsatile gonadotropin secretion, and, in females, a gradual and prolonged oscillating increase in activity responsible for the relatively short-lived preovulatory LH surge. The evidence presented in the study is solid, offering theoretical implications for understanding the behaviour of GnRH neurones in the context of reproductive physiology, and will be of interest to researchers in neuroendocrinology and reproductive biology.

Reviewed by eLife

Exercise training at different intensities induces heat stress, disrupts barrier function and alters microbiota in the gut of mice

1. Puqiao Lian
2. Artemiy Kovynev
3. Lei Wang
4. Amanda CM Pronk
5. Aswin Verhoeven
6. Martin Giera
7. Suzan Thijssen
8. Borja Martínez Téllez
9. Sander Kooijman
10. Patrick CN Rensen
11. Harro Timmerman
12. Harry J Wichers
13. Paul AJ Henricks
14. Gert Folkerts
15. Milena Schönke
16. Saskia Braber

• Curated by eLife

  eLife Assessment

  This valuable study examines how different exercise training intensities affect intestinal barrier function and gut microbiota composition over a 6-week period in mice. The evidence supporting the main claims about exercise-induced intestinal injury and microbiota changes is solid, featuring comprehensive histological analysis, molecular characterization, and metabolomic profiling, though key mechanistic insights and causal relationships remain to be established. The findings have practical implications for understanding exercise-induced gastrointestinal stress, particularly the observation that daily moderate exercise may be more damaging to intestinal integrity than vigorous exercise with rest days. Additional experimental validation would strengthen these conclusions.

Reviewed by eLife

Impaired myofibroblast proliferation is a central feature of pathologic post-natal alveolar simplification

1. Imran S Khan
2. Christopher Molina
3. Xin Ren
4. Vincent C Auyeung
5. Max Cohen
6. Tatsuya Tsukui
7. Amha Atakilit
8. Dean Sheppard

• Curated by eLife

  eLife Assessment

  This study provides important insights into postnatal lung development and the mechanisms underlying bronchopulmonary dysplasia (BPD), a condition with high morbidity and mortality in newborns. Through the use of neonatal hyperoxia, cell-type-specific inactivation of Tgfbr2, and other injury models, the research focuses on the role of TGF-β signaling in BPD pathogenesis, highlighting impaired myofibroblast proliferation as a key factor. The inactivation of Etc2 in Pdgfra-lineaged cells disrupts myofibroblast cytokinesis, leading to alveolar simplification and reduced cell numbers. The use of transgenic mice and single-cell transcriptomics offers a detailed and high-quality dataset, advancing our understanding of BPD and serving as a invaluable resource for developmental biology and neonatal pulmonary research. The study's comprehensive approach, robust data, and methodological rigor make it a compelling contribution to the field, providing both mechanistic insights and a resource for further research into BPD pathogenesis.

Reviewed by eLife