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Advances in Homeostasis and Metabolism in Health and Disease

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Endocrinology and Metabolism".

Deadline for manuscript submissions: closed (20 February 2025) | Viewed by 7915

Special Issue Editor


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Guest Editor
Department of Cellular and Molecular Physiology, Wu Tsai Institute for Mind and Brain, Yale Center for Molecular and Systems Metabolism, Yale University School of Medicine, New Haven, CT 06520, USA
Interests: cardiovascular diseases; nervous system diseases; nutritional and metabolic diseases; neurobiology of homeostasis; neurovascular plasticity; obesity; metabolic syndrome; thermoregulation

Special Issue Information

Dear Colleagues,

Homeostasis, the delicate balance that ensures an organism’s survival by regulating fundamental needs such as food, water, and warmth, profoundly influences behavior and physiology. An intricate network of complex and redundant circuits, both central and peripheral, orchestrates a complex “dance” to meet these survival instincts. Disruptions to those circuits can result in various disorders, affecting the proper functioning of cells, tissues, and organs. Our understanding of the neuronal, metabolic and cellular mechanisms orchestrating homeostasis is far from complete. Obtaining this knowledge will serve as the foundational step to preventing or treating health conditions arising from imbalances in these intricate systems (e.g., obesity).

In this Special Issue of the International Journal of Molecular Sciences, we eagerly invite researchers to submit both original research articles and review papers dedicated to advancing our understanding of the molecular underpinnings of homeostasis in health and unraveling how their disruption contributes to the onset of metabolic diseases.

Dr. Marc Schneeberger
Guest Editor

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Keywords

  • neurobiology of homeostasis
  • peripheral organ metabolism
  • body-brain crosstalk
  • diabetes
  • metabolic syndrome

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Published Papers (3 papers)

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Research

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16 pages, 268 KB  
Article
Inversely Correlated Restoration of Body Condition Score and Systemic Metabolic Burden in Lactating Cows: Implications for Milk Fat Globule Size and Mitigation of Negative Energy Balance Effects on Milk Fat Composition
by Krzysztof Młynek, Kalina Wnorowska, Agata Danielewicz, Antonio Natalello and Kamila Puppel
Int. J. Mol. Sci. 2025, 26(9), 4296; https://doi.org/10.3390/ijms26094296 - 1 May 2025
Cited by 1 | Viewed by 518
Abstract
In lactating dairy cows, negative energy balance (NEB) induces metabolic shifts, including enhanced lipolysis, leading to elevated concentrations of free fatty acids (FFAs) in circulation. Metabolic changes affect milk fat synthesis and the characteristics of milk fat globules (MFGs), particularly their size and [...] Read more.
In lactating dairy cows, negative energy balance (NEB) induces metabolic shifts, including enhanced lipolysis, leading to elevated concentrations of free fatty acids (FFAs) in circulation. Metabolic changes affect milk fat synthesis and the characteristics of milk fat globules (MFGs), particularly their size and distribution. Systemic FFA release inversely correlates with the restoration of the body condition score (BCS), suggesting that recovering the BCS may mitigate the negative effects of NEB on milk fat composition. This study aimed to investigate the relationship between BCS restoration, metabolic burden, and their effects on MFG characteristics in lactating cows. The study was conducted on two dairy farms (F1 and F2) with 80 Holstein-Friesian cows. Cows were grouped according to farm and diet, with average lactation yields of 9653 ± 259 kg (F1) and 9548 ± 341 kg (F2). Milk composition was analyzed, and blood and milk samples were collected at four lactation stages. The results showed a significant correlation between elevated circulating FFA concentrations, resulting from adipose tissue lipolysis during NEB, and alterations in MFG size and distribution. The restoration of BCS was inversely correlated with FFA release, suggesting that improvements in the BCS may mitigate the adverse effects of NEB on milk fat synthesis by regulating lipolysis. Additionally, higher β-hydroxybutyrate (BHBA) levels were associated with a reduction in MFG diameter, indicating disruptions in lipogenesis during metabolic stress. These findings highlight the complex relationship between metabolic stress, BCS restoration, and MFG characteristics, with implications for milk fat synthesis in lactating cows. Full article
(This article belongs to the Special Issue Advances in Homeostasis and Metabolism in Health and Disease)

Review

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22 pages, 2712 KB  
Review
Emerging Role of GCN1 in Disease and Homeostasis
by Yota Tatara, Shuya Kasai, Daichi Kokubu, Tadayuki Tsujita, Junsei Mimura and Ken Itoh
Int. J. Mol. Sci. 2024, 25(5), 2998; https://doi.org/10.3390/ijms25052998 - 5 Mar 2024
Cited by 3 | Viewed by 4398
Abstract
GCN1 is recognized as a factor that is essential for the activation of GCN2, which is a sensor of amino acid starvation. This function is evolutionarily conserved from yeast to higher eukaryotes. However, recent studies have revealed non-canonical functions of GCN1 that are [...] Read more.
GCN1 is recognized as a factor that is essential for the activation of GCN2, which is a sensor of amino acid starvation. This function is evolutionarily conserved from yeast to higher eukaryotes. However, recent studies have revealed non-canonical functions of GCN1 that are independent of GCN2, such as its participation in cell proliferation, apoptosis, and the immune response, beyond the borders of species. Although it is known that GCN1 and GCN2 interact with ribosomes to accomplish amino acid starvation sensing, recent studies have reported that GCN1 binds to disomes (i.e., ribosomes that collide each other), thereby regulating both the co-translational quality control and stress response. We propose that GCN1 regulates ribosome-mediated signaling by dynamically changing its partners among RWD domain-possessing proteins via unknown mechanisms. We recently demonstrated that GCN1 is essential for cell proliferation and whole-body energy regulation in mice. However, the manner in which ribosome-initiated signaling via GCN1 is related to various physiological functions warrants clarification. GCN1-mediated mechanisms and its interaction with other quality control and stress response signals should be important for proteostasis during aging and neurodegenerative diseases, and may be targeted for drug development. Full article
(This article belongs to the Special Issue Advances in Homeostasis and Metabolism in Health and Disease)
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Other

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14 pages, 805 KB  
Opinion
Neuro-Adipokine Crosstalk in Alzheimer’s Disease
by Bandy Chen and Marc Schneeberger
Int. J. Mol. Sci. 2024, 25(11), 5932; https://doi.org/10.3390/ijms25115932 - 29 May 2024
Cited by 3 | Viewed by 2257
Abstract
The connection between body weight alterations and Alzheimer’s disease highlights the intricate relationship between the brain and adipose tissue in the context of neurological disorders. During midlife, weight gain increases the risk of cognitive decline and dementia, whereas in late life, weight gain [...] Read more.
The connection between body weight alterations and Alzheimer’s disease highlights the intricate relationship between the brain and adipose tissue in the context of neurological disorders. During midlife, weight gain increases the risk of cognitive decline and dementia, whereas in late life, weight gain becomes a protective factor. Despite their substantial impact on metabolism, the role of adipokines in the transition from healthy aging to neurological disorders remains largely unexplored. We aim to investigate how the adipose tissue milieu and the secreted adipokines are involved in the transition between biological and pathological aging, highlighting the bidirectional relationship between the brain and systemic metabolism. Understanding the function of these adipokines will allow us to identify biomarkers for early detection of Alzheimer’s disease and uncover novel therapeutic options. Full article
(This article belongs to the Special Issue Advances in Homeostasis and Metabolism in Health and Disease)
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