bims-endanx Biomed News
on Endocrine Anxiety
Issue of 2025–01–12
ten papers selected by
Logan K. Townsend, McMaster University
  1. Time-resolved effects of short-term overfeeding on energy balance in mice.
  2. Effect of proinflammatory cytokines on blood-brain barrier integrity.
  3. Exploring the mechanism and crosstalk between IL-6 and IL- 1β on M2 macrophages under metabolic stress conditions.
  4. An intra-brainstem circuitry for pain-induced inhibition of itch.
  5. The pathobiology of neurovascular aging.
  6. Interaction of the Gut-Liver-Brain Axis and the sterolbiome with sexual dysfunction in patients with cirrhosis.
  7. As different as fear and anxiety: Introducing the fear and anxiety model of placebo hypoalgesia and nocebo hyperalgesia.
  8. Molecular and Functional Significance of Growth Differentiation Factor-15: A Review on Cardiovascular-Kidney-Metabolic Biomarker.
  9. Neural pathways of nausea and roles in energy balance.
  10. Mechanisms and early efficacy data of caloric restriction and caloric restriction mimetics in neurodegenerative disease.
  1. Diabetes. 2025 Jan 09. pii: db240289. [Epub ahead of print]
    Time-resolved effects of short-term overfeeding on energy balance in mice.
    Pablo Ranea-Robles, Camilla Lund, Charlotte Svendsen, Cláudia Gil, Jens Lund, Maximilian Kleinert, Christoffer Clemmensen.
      To curb the obesity epidemic, it is imperative that we improve our understanding of the mechanisms controlling fat mass and body weight regulation. While great progress has been made in mapping the biological feedback forces opposing weight loss, the mechanisms countering weight gain remain less well defined. Here, we integrate a mouse model of intragastric overfeeding with a comprehensive evaluation of the regulatory aspects of energy balance, encompassing food intake, energy expenditure, and fecal energy excretion. Furthermore, to assess the role of adipose tissue thermogenesis in protecting against overfeeding-induced weight gain, we analyze the expression of genes involved in futile metabolic cycles in response to overfeeding and subject uncoupling protein 1 (UCP1) knockout (KO) mice to intragastric overfeeding. Data from two independent experiments demonstrate that 7 days of 140-150% overfeeding results in substantial weight gain and triggers a potent, sustained decrease in voluntary food intake, which coincides with a gradual return of body weight toward baseline after overfeeding. Intragastric overfeeding triggers an increase in energy expenditure that seems to be adaptive. However, mice lacking UCP1 are not impaired in their ability to defend against overfeeding-induced weight gain. Finally, we show that fecal energy excretion decreases in response to overfeeding, but only during the recovery period, driven primarily by a reduction in fecal output rather than in fecal caloric density. In conclusion, while overfeeding may induce adaptive thermogenesis, the primary protective response to forced weight gain in mice appears to be a potent reduction in food intake.
    DOI:  https://doi.org/10.2337/db24-0289
  2. Eur Cytokine Netw. 2024 Sep 01. 35(3): 38-47
    Effect of proinflammatory cytokines on blood-brain barrier integrity.
    Małgorzata Gryka-Marton, Anna Grabowska, Dariusz Szukiewicz.
      The blood-brain barrier (BBB) consists of a unique system of brain microvascular endothelial cells, capillary basement membranes, and terminal branches ("end-feet") of astrocytes. The BBB's primary function is to protect the central nervous system from potentially harmful or toxic substances in the bloodstream by selectively controlling the entry of cells and molecules, including nutrients and immune system components. During neuroinflammation, the BBB loses its integrity, resulting in increased permeability, mostly due to the activity of inflammatory cytokines. However, the pathomechanism of structural and functional changes in the BBB caused by individual cytokines is poorly understood. This review summarizes the current state of knowledge on this topic, which is important from both the pathophysiological and clinical-therapeutic point of view. The structure and function of each of the components of the BBB are discussed with particular attention to phenotypic differences between brain microvascular endothelial cells and the vascular endothelium at other locations of the circulatory system. The protein composition of the inter-endothelial tight junctions in the context of regulating BBB permeability is presented, as is the role of the pericyte-BMEC interaction in the exchange of metabolites, ions, and nucleic acids. Finally, the documented actions of proinflammatory cytokines within the BBB are summarized.
    Keywords:  astrocytes; brain endothelial cells; neuroinflammation; pericyte-endothelial interaction; pericytes; proinflammatory cytokines; tight junctions
    DOI:  https://doi.org/10.1684/ecn.2024.0498
  3. Cytokine. 2025 Jan 06. pii: S1043-4666(24)00356-9. [Epub ahead of print]186 156852
    Exploring the mechanism and crosstalk between IL-6 and IL- 1β on M2 macrophages under metabolic stress conditions.
    Shawna Yadav, Anusha Prasannan, Kaliyamurthi Venkatachalam, Ambika Binesh.
      Macrophages are highly variable immune cells that are important in controlling inflammation and maintaining tissue balance. The ability to polarize into two major types-M1, promoting inflammation, and M2, resolving inflammation and contributing to tissue repair-determines their specific roles in health and disease. M2 macrophages are particularly important for reducing inflammation and promoting tissue regeneration, but their function is shaped mainly by surrounding cells. This is evident in obesity, diabetes, and chronic inflammation. Although many cytokines regulate macrophage polarization, interleukin-6 (IL-6) and interleukin-1β (IL-1β) are major players, but their effects on M2 macrophage behavior under metabolic stress remain unclear. This study describes the intricacies within M2 macrophages concerning IL-6 and IL-1β signaling when under metabolic stress. Though, more frequently than not, IL-6 is labelled as pro-inflammatory, it can also behave as an anti-inflammatory mediator. On the other hand, IL-1β is the main pro-inflammatory agent, particularly in metabolic disorders. The relationship between these cytokines and the macrophages is mediated through important pathways such as JAK/STAT and NFκB, which get perturbed by metabolic stress. Therefore, metabolic stress also alters the functional parameters of macrophages, including alterations in mitochondrial metabolism, glycolytic and oxidative metabolism. Phosphorylation alters the kinetics involved in energy consumption and affects their polarization and their function. However, it has been suggested that IL-6 and IL-1β may work in concert or competition when inducing M2 polarization and, importantly, implicate cytokine release, phagocytic activity, and tissue repair processes. In this review, we discuss the recent literature on the participation of IL-6 and IL-1β cytokines in macrophage polarization and how metabolic stress changes cytokine functions and synergistic relations. A better understanding of these cytokines would serve as an important step toward exploring alternative antiviral strategies directed against metabolic disturbance and, hence, approve further endeavors.
    Keywords:  Interleukin-6; Interleulin-1β; Macrophage polarization and inflammation; Macrophages; Metabolic stress
    DOI:  https://doi.org/10.1016/j.cyto.2024.156852
  4. Neuroscience. 2025 Jan 06. pii: S0306-4522(25)00010-7. [Epub ahead of print]
    An intra-brainstem circuitry for pain-induced inhibition of itch.
    Jagat Narayan Prajapati, Devanshi Piyush Shah, Arnab Barik.
      Pain and itch are unpleasant and distinct sensations that give rise to behaviors such as reflexive withdrawal and scratching in humans and mice. Interestingly, it has been observed that pain modulate itch through the neural circuits housed in the brain and spinal cord. However, we are yet to fully understand the identities of, and mechanisms by which specific neural circuits mediate pain-induced modulation of itch. Independent studies indicate that brainstem nuclei such as the lateral parabrachial nucleus (LPBN) and rostral ventromedial medulla (RVM) are important for the suppression of itch by noxious somatosensory stimuli. Here, using mouse and viral genetics, rabies tracing, chemogenetics, and calcium imaging, we show that the synaptic connections between LPBN and RVM plays an instrumental role in the interactions between pain and itch. Notably, we found that the LPBN neurons that express the gene encoding the substance P receptor, Tacr1 (LPBNTacr1), synapse onto Tacr1-expressing RVM neurons (RVMTacr1). The RVMTacr1 neurons were found to be nociceptive, sufficient for inhibiting itch, and necessary for pain-induced itch suppression. Moreover, through brain-wide anterograde and retrograde viral tracing studies, we found that the RVMTacr1 neurons are bidirectionally connected with LPBN, periaqueductal gray (PAG), and lateral hypothalamic area (LHA). Thus, together, our data indicate that the RVMTacr1 neurons integrate nociceptive information to mediate itch-induced scratching and can mediate the physiological effects of itch through their downstream targets.
    DOI:  https://doi.org/10.1016/j.neuroscience.2025.01.008
  5. Neuron. 2025 Jan 08. pii: S0896-6273(24)00913-9. [Epub ahead of print]113(1): 49-70
    The pathobiology of neurovascular aging.
    Monica M Santisteban, Costantino Iadecola.
      As global life expectancy increases, age-related brain diseases such as stroke and dementia have become leading causes of death and disability. The aging of the neurovasculature is a critical determinant of brain aging and disease risk. Neurovascular cells are particularly vulnerable to aging, which induces significant structural and functional changes in arterial, venous, and lymphatic vessels. Consequently, neurovascular aging impairs oxygen and glucose delivery to active brain regions, disrupts endothelial transport mechanisms essential for blood-brain exchange, compromises proteostasis by reducing the clearance of potentially toxic proteins, weakens immune surveillance and privilege, and deprives the brain of key growth factors required for repair and renewal. In this review, we examine the effects of neurovascular aging on brain function and its role in stroke, vascular cognitive impairment, and Alzheimer's disease. Finally, we discuss key unanswered questions that must be addressed to develop neurovascular strategies aimed at promoting healthy brain aging.
    Keywords:  Alzheimer’s disease; blood-brain barrier; neurovascular unit; neurovasculome; rejuvenation strategies; vascular cognitive impairment
    DOI:  https://doi.org/10.1016/j.neuron.2024.12.014
  6. Gut Microbes. 2025 Dec;17(1): 2446390
    Interaction of the Gut-Liver-Brain Axis and the sterolbiome with sexual dysfunction in patients with cirrhosis.
    Spencer C Harris, Jasmohan S Bajaj.
      There is a complex interplay between the gut microbes, liver, and central nervous system, a gut-liver-brain axis, where the brain impacts intestinal and hepatic function while the gut and liver can impact cognition and mental status. Dysregulation of this axis can be seen in numerous diseases. Hepatic encephalopathy, a consequence of cirrhosis, is perhaps the best studied perturbation of this system. However, patients with cirrhosis have been shown to have increased incidence of other disorders of mental health which may be otherwise less clinically identifiable. Sexual dysfunction affects a large proportion of patients with cirrhosis and is associated with decreased quality of life. Screening for sexual dysfunction in patients with cirrhosis is often overlooked, and even when identified, treatment options are limited, particularly in patients with advanced liver disease. The mechanism by which patients with cirrhosis develop sexual dysfunction is multifactorial, but a key driver of this clinical manifestation is alterations in circulating sex hormones. In patients with cirrhosis, low serum sex hormones have been shown to be associated with higher mortality regardless of MELD score. The gut microbiome has been shown to have an immense metabolic capacity to metabolize steroid hormones. This "sterolbiome" has already been implicated in other disease processes and has been linked to low circulating sex hormones, suggesting a new mechanism by which sex hormones may be altered in disease states where the gut-liver-brain axis is disrupted. The aim of this review is to cover sex hormone changes and sexual dysfunction in cirrhosis, examine the gut microbiome and its metabolic capacity, particularly for steroid hormones, and consider how microbial changes using fecal microbiota transplant could modulate sexual dysfunction.
    Keywords:  alcohol; fecal microbiota transplant; gut-liver-brain axis; hepatic encephalopathy; obesity; sex hormone
    DOI:  https://doi.org/10.1080/19490976.2024.2446390
  7. Psychol Rev. 2025 Jan 06.
    As different as fear and anxiety: Introducing the fear and anxiety model of placebo hypoalgesia and nocebo hyperalgesia.
    Daryna Rubanets, Julia Badzińska, Sofiia Honcharova, Przemysław Bąbel, Elżbieta A Bajcar.
      Research suggests that negative affective states, such as fear and anxiety that accompany placebo treatment may be considered predictors of placebo hypoalgesia and nocebo hyperalgesia. There is also data showing that the likelihood of developing nocebo hyperalgesia is related to the relatively stable tendency to experience these negative emotions. We aimed to summarize the current state-of-the-art in studies and theoretical models on the role of fear and anxiety in placebo hypoalgesia/nocebo hyperalgesia, with a clear differentiation between these emotions. The role of fear and anxiety accompanying placebo treatment in shaping placebo effects is often studied, but less attention has been given to pretreatment emotional states. We propose a model that combines knowledge from the emotional and pain paradigms with the current research on placebo hypoalgesia and nocebo hyperalgesia to present the involvement of fear and anxiety as traits, as well as pretreatment and posttreatment states of fear and anxiety to placebo effects. The main assumption of the model is that trait fear, trait anxiety, and related pretreatment affective states impact pain perception differently. Heightened fear is associated with decreased pain perception, while heightened anxiety is linked to increased pain perception. Consequently, heightened pretreatment fear may lead to reduced nocebo hyperalgesia and enhanced placebo hypoalgesia, while heightened pretreatment anxiety may result in decreased placebo hypoalgesia and increased nocebo hyperalgesia. In conclusion, we propose future research directions and clinical applications of the model. (PsycInfo Database Record (c) 2025 APA, all rights reserved).
    DOI:  https://doi.org/10.1037/rev0000521
  8. Curr Cardiol Rev. 2025 Jan 07.
    Molecular and Functional Significance of Growth Differentiation Factor-15: A Review on Cardiovascular-Kidney-Metabolic Biomarker.
    Krishna Tiwari, Aswini Saravanan, Abhishek Anil, Vikas Kumar Tiwari, Muhammad Aaqib Shamim, Surjit Singh, Pradeep Dwivedi, Surender Deora, Shoban Babu Varthya.
      Cardiovascular-kidney-metabolic (CKM) syndrome is the association between obesity, diabetes, CKD (chronic kidney disease), and cardiovascular disease. GDF-15 mainly acts through the GFRAL (Glial cell line-derived neurotrophic factor Family Receptor Alpha-Like) receptor. GDF-15 and GDFRAL complex act mainly through RET co-receptors, further activating Ras and phosphatidylinositol-3-kinase (PI3K)/Akt pathways through downstream signaling. GDF-15 decreases cardiac dysfunction and hypertrophy by inducing HIF-α (hypoxia-inducible factor-1α). It causes increased fractional shortening and a significant decrease in ventricular dilation through the induction of the SMAD 2/3. GDF-15 prevents hyperglycemia-induced apoptosis in diabetes mellitus. GDF-15 causes anorexia by influencing the central systems regulating metabolism and appetite. Therefore, targeting GDF-15 can be useful for the treatment of anorexia caused by cancer as well as the prevention of resulting weight loss. GDF-15 has an important role in predicting mortality in acute kidney injury. Its high levels are related to eGFR decline and also have a prognostic role in CKD patients. Growth differentiation factor-15 (GDF-15) is a vital biomarker for diagnosis, treatment, and prognosis of CKM syndrome. Elevated GDF-15 levels can be utilised as a biomarker to determine the suitable metformin dosage. In light chain amyloidosis, a raised level of GDF-15 predicts early death in heart failure and renal disease patients. In vivo, studies using GDF-15 analogs and antibodies against GFRAL to affect metabolic parameters and ventricular dilatation have shown potential for GDF-15-based therapeutic interventions. This review aims to study the role of GDF-15 in CKM syndrome and establish it as a CKM biomarker.
    Keywords:  Cardiovascular- kidney-metabolic syndrome.; GDF-15; cellular functions; diagnostic marker; molecular functions; prognostic marker; therapeutic target
    DOI:  https://doi.org/10.2174/011573403X332671241121063641
  9. Curr Opin Neurobiol. 2025 Jan 06. pii: S0959-4388(24)00125-9. [Epub ahead of print]90 102963
    Neural pathways of nausea and roles in energy balance.
    Chuchu Zhang.
      Our internal sensory systems encode various gut-related sensations, such as hunger, feelings of fullness, and nausea. These internal feelings influence our eating behaviors and play a vital role in regulating energy balance. Among them, the neurological basis for nausea has been the least well characterized, which has hindered comprehension of the connection between these sensations. Single-cell sequencing, along with functional mapping, has brought clarity to the neural pathways of nausea involving the brainstem area postrema. In addition, the newly discovered nausea sensory signals have deepened our understanding of the area postrema in regulating feeding behaviors. Nausea has significant clinical implications, especially in developing drugs for weight loss and metabolism. This review summarizes recent research on the neural pathways of nausea, particularly highlighting their contribution to energy balance.
    DOI:  https://doi.org/10.1016/j.conb.2024.102963
  10. Neuroscience. 2025 Jan 04. pii: S0306-4522(25)00006-5. [Epub ahead of print]
    Mechanisms and early efficacy data of caloric restriction and caloric restriction mimetics in neurodegenerative disease.
    Anchal Trisal, Abhishek Kumar Singh.
      Neurodegenerative disorders (NDDs) have been prevalent for more than a decade, and the number of individuals affected per year has increased exponentially. Among these NDDs, Alzheimer's disease, which causes extreme cognitive impairment, and Parkinson's disease, characterized by impairments in motor activity, are the most prevalent. While few treatments are available for clinical practice, they have minimal effects on reversing the neurodegeneration associated with these debilitating diseases. Lifestyle modifications and dietary choices are emerging and promising approaches to combat these disorders. Of the lifestyle changes that one could adopt, a major habit is caloric restriction. Caloric restriction (CR) is a lifestyle modification in which the amount of calories ingested is reduced to a significant amount without resulting in malnutrition. However, maintaining such a lifestyle is challenging. As alternatives, certain compounds have been recognized to mimic the effects produced by CR. These compounds are called caloric restriction mimetics (CRMs). Among these compounds, some have been designated established CRMs, namely, resveratrol, metformin, and rapamycin, whereas several other candidates are termed potential CRMs because of a lack of conclusive evidence of their effects. The potential CRMs discussed in this review are quercetin, chrysin, astragalin, apigenin, curcumin, epigallocatechin-3-gallate, and NAD+ precursors. This review aims to provide an overview of these CRMs' effectiveness in preventing neurodegenerative disorders associated with aging. Moreover, we highlight the clinical relevance of these compounds by discussing in detail the results of clinical trials on them.
    Keywords:  Alzheimer’s disease; Caloric restriction mimetics; Clinical trials; Parkinson’s disease; Preclinical studies
    DOI:  https://doi.org/10.1016/j.neuroscience.2025.01.004
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