Physiology

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 investigates the function of Chi3l1 in hepatic macrophages in the context of MASLD, providing useful insights at a time when the distinct roles of Kupffer cells or monocyte-derived macrophages in this disease remain incompletely defined. The data suggests that CHI3L1 in Kupffer cells modulates glucose handling in obesity and mitigates systemic metabolic dysfunction and hepatic steatosis during high-fat, high-fructose feeding. However, the loss-of-function studies employing Kupffer cell restricted versus a pan myeloid Cre lines are not sufficient to support the assertion that CHI3L1 activity is confined to resident Kupffer cells. Additionally, the flow-cytometric analyses reveal a modest depletion of Kupffer cells and no recruitment of TIM4low monocyte-derived macrophages, indicating that the system reflects simple steatosis rather than substantial macrophage turnover or niche remodelling. While the findings are intriguing, further experimentation is required to clarify the cellular specificity and mechanistic basis of the phenotypes observed.

Reviewed by eLife

Sex-biased expression of enteroendocrine cell-derived hormones contributes to higher fat storage in Drosophila females

1. Puja Biswas
2. Elizabeth J Rideout

• Curated by eLife

  eLife Assessment

  This useful study provides a systematic and solid comparison of sex-biased enteroendocrine peptide expression, including AstC and Tk, to show that these peptides contribute to female-biased fat storage. The major research question of this study is based on the authors' previous papers, and therefore, the presented results are incremental. This study serves as a foundation for future investigation of regulatory mechanisms for the sex-biased fat content by AstC and Tk.

Reviewed by eLife

PIEZO channels link mechanical forces to uterine contractions in parturition

1. Yunxiao Zhang
2. Sejal A. Kini
3. Sassan A. Mishkanian
4. Renhao Luo
5. Saba Heydari Seradj
6. Verina H. Leung
7. Yu Wang
8. M. Rocío Servín-Vences
9. William T. Keenan
10. Utku Sonmez
11. Oleg Yarishkin
12. Manuel Sanchez-Alavez
13. Yuejia Liu
14. Xin Jin
15. Darren J. Lipomi
16. Li Ye
17. Michael Petrascheck
18. Antonina I. Frolova
19. Sarah K. England
20. Ardem Patapoutian

Reviewed by PREreview

Roles of G-protein coupled receptors and mechanosensitive ion channels in pressure-induced chronotropy of lymphatic vessels

1. Michael J Davis
2. Hae Jin Kim
3. Min Li
4. Jorge A Castorena-Gonzalez
5. Soumiya Pal
6. Timothy L Domeier
7. Joshua P Scallan
8. Scott Earley
9. Scott D Zawieja

• Curated by eLife

  eLife Assessment

  Davis and colleagues describe findings that are fundamental to the understanding of pressure mechanosensation in lymphatic vessels and are of significant importance to other areas of mechanosensory physiology. Based on many different knockout mouse models and rigorous state-of-the-art pressure myography recordings, they present compelling evidence that mechano-activation of GNAQ/GNA11-coupled GPCRs generates IP3, which induces Ca2+ release from internal stores through IP3R1 and drives depolarization through the activation of ANO1 Cl- channels to induce lymphatic vessel contractility. Nevertheless, some aspects of the manuscript are incomplete. The specific identity of the GPCR(s) involved remains to be uncovered, as evidence of frequency-pressure impairment is only demonstrated with abolition of GNAQ/GNA11action, not the receptors per se.

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 PREreview

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

1. Sönke Cordeiro
2. Robert Patejdl
3. Thomas Baukrowitz
4. Marianne 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; macroscopic currents and single-channel experiments show that α-mangostin produces an increase in the probability of opening, without affecting the single-channel conductance. The authors put forward 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

Non-visual light modulates behavioral memory and gene expression in C. elegans

1. Zhijian Ji
2. Bingying Wang
3. Rashmi Chandra
4. Junqiang Liu
5. Supeng Yang
6. Yong Long
7. Michael Egan
8. Noelle L’Etoile
9. Dengke K Ma

• Curated by eLife

  eLife Assessment

  This important study uncovers a previously unrecognized light-responsive pathway in C. elegans, centred on ZIP-2/CEBP-2 and the cytochrome P450 enzyme CYP-14A5. The pathway operates independently of known photoreceptors, modulates long-term memory, and can be harnessed as a low-cost light-inducible expression system, opening new directions for sensory biology and genetic engineering in worms. The strength of evidence is compelling if a bacterially derived stimulus is ruled out. Multiple genetic, transcriptional, and behavioural assays support the pathway's role, but a decisive test showing that the initiating light cue is worm-intrinsic rather than mediated by changes in the bacterial food source is still needed.

Reviewed by eLife

Progressive postnatal hearing development limits early parent-offspring vocal communication in the zebra finch

1. Tommi Anttonen
2. Jakob Christensen-Dalsgaard
3. Coen PH Elemans

• Curated by eLife

  eLife Assessment

  Zebra finches are a prominent model system for vocal learning and auditory system function, yet little is known about the functional development of the auditory system. Here, the authors convincingly show that newly hatched zebra finches lack detectable auditory brainstem responses and that auditory neural signals emerge only days after hatching, challenging influential claims of prenatal acoustic communication in altricial birds. This important work clarifies the developmental timeline for auditory communication and highlights the value of neuroscientific methods for validating and complementing behavioral ecological studies of animal perception.

Reviewed by eLife

NAD+ boosting by oral nicotinamide mononucleotide administration regulates key metabolic and immune pathways through SIRT1 dependent and independent mechanisms to mitigate diet-induced obesity and dyslipidemia in mice

1. Yasser Majeed
2. Najeeb M Halabi
3. Rudolf Engelke
4. Hina Sarwath
5. Muna N Al-Noubi
6. Sunkyu Choi
7. Aisha Al-Malki
8. Maha V Agha
9. Muneera Vakayil
10. Lotfi Chouchane
11. Frank Schmidt
12. Nayef A Mazloum

• Curated by eLife

  eLife Assessment

  The mechanistic basis for the potential health benefits of NAD⁺ precursors remains incompletely understood. This manuscript provides a useful assessment of the role of SIRT1 in mediating the effects of NMN in mice fed a high-fat diet. The study addresses a key question, though some of the conclusions appear only partially supported by the presented data.

Reviewed by eLife

The titin N2A-MARP signalosome constrains muscle longitudinal hypertrophy in response to stretch

1. Robbert van der Pijl
2. Jochen Gohlke
3. Joshua Strom
4. Eva Peters
5. Shengyi Shen
6. Stefan Conijn
7. Zaynab Hourani
8. Stephan Lange
9. Ju Chen
10. Paul Langlais
11. Siegfried Labeit
12. Henk Granzier
13. Coen Ottenheijm

• Curated by eLife

  eLife Assessment

  The study presents important insights into the regulation of muscle hypertrophy, regulated by Muscle Ankyrin Repeat Proteins (MARPs) and mTOR. The methods are overall solid and complementary, with only minor limitations. Overall, the findings will be of interest for both muscle-biology specialists and the broader mechanobiology community.

Reviewed by eLife