Physiology

Modeling metabolic disease susceptibility and resilience in genetically diverse mice

1. Candice N Baker
2. Jeffrey M Harder
3. Daniel A Skelly
4. Isabella Gerdes Gyuricza
5. Margaret Gaca
6. Matthew Vincent
7. Allison Ingalls
8. Mark P Keller
9. Alan D Attie
10. Madeleine Braun
11. Michael Stitzel
12. Edison T Liu
13. Nadia Rosenthal
14. Gary A Churchill

• Curated by eLife

  eLife Assessment

  The authors used three genetically diverse mouse models to investigate the impact of genome diversity on metabolic disease outcomes, such as obesity and glucose tolerance. This study is important because it integrates comprehensive metabolic analyses and multi-tissue phenotyping across sexes to reveal pathways relevant to obesity and its complications; the data are convincing and uncover several pathways that advance understanding of disease etiology while suggesting potential therapeutic avenues to prevent obesity-related health risks. There are limitations, such as a limited number of mouse strains used in the work, the 9-week feeding regime may be too short to capture full metabolic remodeling, and the mechanisms by which the immune-adipose axis impacts the broader phenotype are not fully described. Overall, the study is compelling, but the manuscript could be improved by justifying the strain selection, addressing the concern about the feeding duration, and providing stronger mechanistic support or discussion.

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:

  In this revised version, the authors provide a thorough investigation of the interaction of megakaryocytes (MK) with their associated extracellular matrix (ECM) during maturation; they provide compelling 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 conclusion is based on the use of state-of-the art techniques such f 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 eLife, preLights

The denitrosylase SCoR2 controls cardioprotective metabolic reprogramming

1. Zachary W Grimmett
2. Rongli Zhang
3. Hua-Lin Zhou
4. Qiuying Chen
5. Dawson Miller
6. Zhaoxia Qian
7. Justin Lin
8. Riti Kalra
9. Steven S Gross
10. Walter J Koch
11. Richard T Premont
12. Jonathan S Stamler

• Curated by eLife

  eLife Assessment

  This study provides new and interesting findings that SCoR2 acts as a denitrosylase to control cardioprotective metabolic reprogramming and prevent injury following ischemia/reperfusion. The compelling evidence is supported by a novel multi-omics approach, but questions remain regarding the stability and human relevance of BDH1 as well as the sufficiency of SCoR2. Overall, the work will be of interest to cardiovascular researchers and provides useful information to the field, though some mechanistic aspects require further clarification.

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. These findings shed light on an adaptive strategy to integrate food perception with physiological responses, with a mix of solid and convincing evidence supporting the work.

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 that demonstrates that 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 evidence is compelling whereby the authors use appropriate and validated methodology in line with or more rigorous than the current state-of-the-art.

Reviewed by eLife

The hypoxic response extends lifespan through a bioaminergic and peptidergic neural circuit

1. Elizabeth S Kitto
2. Shijiao Huang
3. Mira Bhandari
4. Cassie Tian
5. Rebecca L Cox
6. Safa Beydoun
7. Emily Wang
8. Danielle Shave
9. Hillary A Miller
10. Sarah A Easow
11. Ella Henry
12. Megan L Schaller
13. Scott F Leiser

• Curated by eLife

  eLife Assessment

  This fundamental study identifies specific neural mechanisms through which HIF-1 signaling in ADF serotonergic neurons extends lifespan in C. elegans, revealing that downstream signaling in multiple types of neurons, as well as other neuromodulators like GABA, tyramine, and NLP-17, is required for this effect. The strength of the evidence is largely convincing, as the authors establish the necessity and causality of key neuronal components using multiple genetic tools and functional dissection in a well-validated model organism.

Reviewed by eLife

SLC4A1 mutations that cause distal renal tubular acidosis alter cytoplasmic pH and cellular autophagy

1. Grace Essuman
2. Midhat Rizvi
3. Ensaf Almomani
4. Shahid AK M Ullah
5. Sarder MA Hasib
6. Forough Chelangarimiyandoab
7. Priyanka Mungara
8. Manfred J Schmitt
9. Marguerite Hureaux
10. Rosa Vargas-Poussou
11. Nicolas Touret
12. Emmanuelle Cordat

• Curated by eLife

  eLife Assessment

  This work characterizes the function and localization of SLC4A1 variants associated with distal renal tubular acidosis in human patients. Cell culture and limited animal studies provide partial but incomplete support to the authors' claim that the variants disrupt normal protein degradative flux by alkalinizing the intracellular pH. The study is valuable in providing preliminary evidence for future exploration of the link between intracellular pH regulation by SLC4A1 and kidney cell function in vivo.

Reviewed by eLife

Loss of the alternative calcineurin variant CnAβ1 enhances brown adipocyte differentiation and drives metabolic overactivation through FoxO1 activation

1. Elísabet Bello-Arroyo
2. Blanca Rubio
3. Alfonso Mora
4. Marina López-Olañeta
5. Jesús M. Gómez-Salinero
6. Laura Ramos
7. Carlos G. Sánchez-Cabezudo
8. Emilio Camafeita
9. Lorena Cusso
10. Manuel Desco
11. Nolwenn Joffin
12. Johanne Le Coq
13. Jasminka Boskovic
14. Kathryn A. McGurk
15. James S. Ware
16. Paul J. R. Barton
17. Jesús Vázquez
18. Philipp E. Scherer
19. Guadalupe Sabio
20. María Victoria Gómez-Gaviro
21. Enrique Lara-Pezzi

Reviewed by Review Commons

Transient hypoxia followed by progressive reoxygenation is required for efficient skeletal muscle repair through Rev-ERBα modulation

1. Marie Quétin
2. Audrey Der Vartanian
3. Christelle Dubois
4. Juliette Berthier
5. Marine Ledoux
6. Stéphanie Michineau
7. Bernadette Drayton-Libotte
8. Athanassia Sotiropoulos
9. Frédéric Relaix
10. Marianne Gervais

Reviewed by Review Commons

Probing relaxed myosin states in hypertrophic cardiomyopathy by second harmonic-generation microscopy

1. Giulia Arecchi
2. Marica Dente
3. Weikang Ma
4. Beatrice Scellini
5. Nicoletta Piroddi
6. Marina Scardigli
7. Jingyuan Yu
8. Jing Zhao
9. Riccardo Cicchi
10. Ryo Kinegawa
11. Caroline Muellenbroich
12. Corrado Poggesi
13. Cecilia Ferrantini
14. Thomas C Irving
15. Michael Regnier
16. Leonardo Sacconi
17. Chiara Tesi

• Curated by eLife

  eLife Assessment

  Arecchi et al. demonstrate that polarized second-harmonic generation microscopy can be used to probe the ON/OFF states of myosin in both permeabilized and intact muscle, making this key measurement accessible to a greater number of labs. This has the potential to help with the study of disease-causing mutations and our understanding of drug function. The methodology is well defined, and the results are important; however, whilst this is overall a convincing study, there are some limitations to the interpretation of the data.

Reviewed by eLife