bims-endanx 2025-02-16 papers

bims-endanx

Biomed News

on Endocrine Anxiety

Issue of 2025–02–16
eight papers selected by
Logan K. Townsend, McMaster University

Impact of physical activity on physical function, mitochondrial energetics, ROS production, and Ca2+ handling across the adult lifespan in men.
Stress-Free Voluntary Exercise Promotes Prophylactic Enhancement of Stress Resilience via the Nucleus Reuniens Affecting the Medial Prefrontal Cortex-Hippocampal Pathway.
Hunger Games: A Modern Battle Between Stress and Appetite.
GDF15 blockade can reduce immunotherapy resistance in urothelial cancer.
Mechanotransduction in the Perivascular Adipose Tissue.
Understanding the desire for dessert.
Immune Regulatory Crosstalk in Adipose Tissue Thermogenesis.
Macrophages protect against sensory axon loss in peripheral neuropathy.

Cell Rep Med. 2025 Feb 06. pii: S2666-3791(25)00041-2. [Epub ahead of print] 101968

Impact of physical activity on physical function, mitochondrial energetics, ROS production, and Ca2+ handling across the adult lifespan in men.

Marina Cefis, Vincent Marcangeli, Rami Hammad, Jordan Granet, Jean-Philippe Leduc-Gaudet, Pierrette Gaudreau, Caroline Trumpff, Qiuhan Huang, Martin Picard, Mylène Aubertin-Leheudre, Marc Bélanger, Richard Robitaille, José A Morais, Gilles Gouspillou.

  Aging-related muscle atrophy and weakness contribute to loss of mobility, falls, and disability. Mitochondrial dysfunction is widely considered a key contributing mechanism to muscle aging. However, mounting evidence positions physical activity as a confounding factor, making unclear whether muscle mitochondria accumulate bona fide defects with aging. To disentangle aging from physical activity-related mitochondrial adaptations, we functionally profiled skeletal muscle mitochondria in 51 inactive and 88 active men aged 20-93. Physical activity status confers partial protection against age-related decline in physical performance. Mitochondrial respiration remains unaltered in active participants, indicating that aging per se does not alter mitochondrial respiratory capacity. Mitochondrial reactive oxygen species (ROS) production is unaffected by aging and higher in active participants. In contrast, mitochondrial calcium retention capacity decreases with aging regardless of physical activity and correlates with muscle mass, performance, and the stress-responsive metabokine/mitokine growth differentiation factor 15 (GDF15). Targeting mitochondrial calcium handling may hold promise for treating aging-related muscle impairments.

Keywords:  calcium retention capacity; functional capacities; intermuscular fat accumulation; mitochondria; mitochondrial permeability transition pore; muscle atrophy and weakness; physical performance; reactive oxygen species; sarcopenia; skeletal muscle aging

DOI:  https://doi.org/10.1016/j.xcrm.2025.101968
Med Sci Sports Exerc. 2025 Feb 12.

Stress-Free Voluntary Exercise Promotes Prophylactic Enhancement of Stress Resilience via the Nucleus Reuniens Affecting the Medial Prefrontal Cortex-Hippocampal Pathway.

Dong-Joo Hwang, Joon-Yong Cho.

PURPOSE: Stress is a risk factor for psychiatric illnesses. However, not all individuals exposed to stress will develop affective disorders. We examined whether pretreatment with stress-free voluntary wheel running (VWR) exercise prophylactically enhances stress resilience in rodents and how it can effectively prevent the development of depressive- and anxiety-like behaviors.
METHODS: Eight-week-old C57BL6/J mice were housed in cages with VWR and subjected to chronic restraint stress (CRST) for 2 h daily for 14 days. The mice were assessed for depressive- and anxiety-like behaviors, and a behavioral matrix (k-means clustering) was introduced to segregate the mice into susceptible and resilient subpopulations. Chemogenetic inhibition and retrograde tracing were used to map the neural circuits involved in VWR's resilience-enhancing properties.
RESULTS: After CRST exposure, 71.50% of CRST mice with VWR were stress resilient, with less stress-induced prolonged activation of the hypothalamic-pituitary-adrenal (HPA) axis and corticosterone (CORT) response, representing a 57.20% increase compared with CRST-only mice. Staining for c-Fos showed that VWR activated predominantly hippocampal GABAergic neurons and suppressed the activity in the medial prefrontal cortex (mPFC). Chemogenetic inhibition of the ventral hippocampus (vHPC) dissipated the antidepressant and anxiolytic effects of VWR pretreatment. In addition, the nucleus reuniens (NR) was implicated in VWR's resilience-enhancing properties, relaying reciprocal interactions of the mPFC-vHPC pathway.
CONCLUSIONS: These findings suggest that stress-free voluntary exercise may be an effective modality for stress management and warrant further investigation into its resilience-enhancing mechanisms.

DOI: https://doi.org/10.1249/MSS.0000000000003672
J Neurochem. 2025 Feb;169(2): e70006

Hunger Games: A Modern Battle Between Stress and Appetite.

Whitnei Smith, Estefania P Azevedo.

  Stress, an evolutionarily adaptive mechanism, has become a pervasive challenge in modern life, significantly impacting feeding-relevant circuits that play a role in the development and pathogenesis of eating disorders (EDs). Stress activates the hypothalamic-pituitary-adrenal (HPA) axis, disrupts specific neural circuits, and dysregulates key brain regions, including the hypothalamus, hippocampus, and lateral septum. These particular structures are interconnected and key in integrating stress and feeding signals, modulating hunger, satiety, cognition, and emotional coping behaviors. Here we discuss the interplay between genetic predispositions and environmental factors that may exacerbate ED vulnerability. We also highlight the most commonly used animal models to study the mechanisms driving EDs and recent rodent studies that emphasize the discovery of novel cellular and molecular mechanisms integrating stress and feeding signals within the hippocampus-lateral septum-hypothalamus axis. In this review, we discuss the role of gut microbiome, an emerging area of research in the field of EDs and unanswered questions that persist and hinder the scientific progress, such as why some individuals remain resilient to stress while others become at high risk for the development of EDs. We finally discuss the need for future research delineating the impact of specific stressors on neural circuits, clarifying the relevance and functionality of hippocampal-septal-hypothalamic connectivity, and investigating the role of key neuropeptides such as CRH, oxytocin, and GLP-1 in human ED pathogenesis. Emerging tools like single-cell sequencing and advanced human imaging could uncover cellular and circuit-level changes in brain areas relevant for feeding in ED patients. Ultimately, by integrating basic and clinical research, science offers promising avenues for developing personalized, mechanism-based treatments targeting maladaptive eating behavior for patients suffering from EDs.

Keywords:  circuits; eating disorders; feeding; stress

DOI:  https://doi.org/10.1111/jnc.70006
Nat Rev Urol. 2025 Feb 11.

GDF15 blockade can reduce immunotherapy resistance in urothelial cancer.

Maria Chiara Masone.

DOI: https://doi.org/10.1038/s41585-025-01005-x
Arterioscler Thromb Vasc Biol. 2025 Feb 13.

Mechanotransduction in the Perivascular Adipose Tissue.

Stephanie W Watts, Teresa Krieger-Burke, Rance Nault, G Andres Contreras.

  Perivascular adipose tissue is of compelling interest when considering tissue mechanotransduction. Because of its location around a vessel, perivascular adipose tissue experiences from high (artery) to low (vein) pressures, pressures that are cyclical in nature. With blood pressure change, such as the elevation of pressure in hypertension, the question has been raised as to whether perivascular adipose tissue senses such changes, evidenced by a response that can be genetic, structural, or mechanical in nature. Here, we briefly review the following knowledge and data that support the ability of perivascular adipose tissue to both (mechano)sense and (mechano)respond.

Keywords:  adipose tissue; arteries; blood pressure; hypertension; mechanotransduction, cellular

DOI:  https://doi.org/10.1161/ATVBAHA.124.321688
Science. 2025 Jan 02. 387(6735): 717-718

Understanding the desire for dessert.

Sadaf Farooqi.

A neural circuit in mice mediates the preference for high-sugar food after a meal.

DOI: https://doi.org/10.1126/science.adv4359
Compr Physiol. 2025 Feb;15(1): e70001

Immune Regulatory Crosstalk in Adipose Tissue Thermogenesis.

Ramazan Yildiz, Khatanzul Ganbold, Njeri Z R Sparman, Prashant Rajbhandari.

Brown adipose tissue (BAT) and thermogenic beige fat within white adipose tissue (WAT), collectively known as adaptive thermogenic fat, dissipate energy as heat, offering promising therapeutic potential to combat obesity and metabolic disorders. The specific biological functions of these fat depots are determined by their unique interaction with the microenvironments, composed of immune cells, endothelial cells, pericytes, and nerve fibers. Immune cells residing in these depots play a key role in regulating energy expenditure and systemic energy homeostasis. The dynamic microenvironment of thermogenic fat depots is essential for maintaining tissue health and function. Immune cells infiltrate both BAT and beige WAT, contributing to their homeostasis and activation through intricate cellular communications. Emerging evidence underscores the importance of various immune cell populations in regulating thermogenic adipose tissue, though many remain undercharacterized. This review provides a comprehensive overview of the immune cells that regulate adaptive thermogenesis and their complex interactions within the adipose niche, highlighting their potential to influence metabolic health and contribute to therapeutic interventions for obesity and metabolic syndrome.

DOI: https://doi.org/10.1002/cph4.70001
Nature. 2025 Feb 12.

Macrophages protect against sensory axon loss in peripheral neuropathy.

Sara Hakim, Aakanksha Jain, Stuart S Adamson, Veselina Petrova, Jonathan Indajang, Hyoung Woo Kim, Riki Kawaguchi, Qing Wang, Elif S Duran, Drew Nelson, Caitlin A Greene, Jenae Rasmussen, Clifford J Woolf.

Peripheral neuropathy is a common complication of type 2 diabetes, which is strongly associated with obesity1, causing sensory loss and, in some patients, neuropathic pain2,3. Although the onset and progression of diabetic peripheral neuropathy is linked with dyslipidaemia and hyperglycaemia4, the contribution of inflammation to peripheral neuropathy pathogenesis has not been investigated. Here we used a high-fat, high-fructose diet (HFHFD), which induces obesity and prediabetic metabolic changes, to study the onset of peripheral neuropathy. Mice fed the HFHFD developed persistent heat hypoalgesia after 3 months, but a reduction in epidermal skin nerve fibre density manifested only at 6 months. Using single-cell sequencing, we found that CCR2+ macrophages infiltrate the sciatic nerves of HFHFD-fed mice well before axonal degeneration is detectable. These infiltrating macrophages share gene expression similarities with nerve-crush-induced macrophages5 and express neurodegeneration-associated microglial marker genes6, although there is no axon loss or demyelination. Inhibiting the macrophage recruitment by genetically or pharmacologically blocking CCR2 signalling resulted in more severe heat hypoalgesia and accelerated skin denervation, as did deletion of Lgals3, a gene expressed in recruited macrophages. Recruitment of macrophages into the peripheral nerves of obese prediabetic mice is, therefore, neuroprotective, delaying terminal sensory axon degeneration by means of galectin 3. Potentiating and sustaining early neuroprotective immune responses in patients could slow or prevent peripheral neuropathy.

DOI: https://doi.org/10.1038/s41586-024-08535-1