scholarly journals mTOR Pathway is Involved in Energy Homeostasis Regulation as a Part of the Gut–Brain Axis

2020 ◽  
Vol 21 (16) ◽  
pp. 5715
Author(s):  
Veronica Pena-Leon ◽  
Raquel Perez-Lois ◽  
Luisa Maria Seoane
Keyword(s):  
Energy Homeostasis ◽  
The Body ◽  
Mtor Signaling ◽  
Physiological Processes ◽  
Energy Sensor ◽  
Relevant Role ◽  
Regulate Food Intake ◽  
Glucose And Lipid Homeostasis ◽  
Treatment Of Obesity

Mammalian, or mechanic, target of rapamycin (mTOR) signaling is a crucial factor in the regulation of the energy balance that functions as an energy sensor in the body. The present review explores how the mTOR/S6k intracellular pathway is involved in modulating the production of different signals such as ghrelin and nesfatin-1 in the gastrointestinal tract to regulate food intake and body weight. The role of gastric mTOR signaling in different physiological processes was studied in depth through different genetic models that allow the modulation of mTOR signaling in the stomach and specifically in gastric X/A type cells. It has been described that mTOR signaling in X/A-like gastric cells has a relevant role in the regulation of glucose and lipid homeostasis due to its interaction with different organs such as liver and adipose tissue. These findings highlight possible therapeutic strategies, with the gut–brain axis being one of the most promising targets in the treatment of obesity.

scholarly journals Appetite control

2005 ◽  
Vol 184 (2) ◽  
pp. 291-318 ◽  
Author(s):  
Katie Wynne ◽  
Sarah Stanley ◽  
Barbara McGowan ◽  
Steve Bloom
Keyword(s):  
Energy Homeostasis ◽  
Gut Hormones ◽  
The Body ◽  
Appetite Control ◽  
Homeostatic Process ◽  
The Past ◽  
Regulate Food Intake ◽  
Treatment Of Obesity ◽  
Physiological Systems

Our understanding of the physiological systems that regulate food intake and body weight has increased immensely over the past decade. Brain centres, including the hypothalamus, brainstem and reward centres, signal via neuropeptides which regulate energy homeostasis. Insulin and hormones synthesized by adipose tissue reflect the long-term nutritional status of the body and are able to influence these circuits. Circulating gut hormones modulate these pathways acutely and result in appetite stimulation or satiety effects. This review discusses central neuronal networks and peripheral signals which contribute energy homeostasis, and how a loss of the homeostatic process may result in obesity. It also considers future therapeutic targets for the treatment of obesity.

Pathogenesis as a problem of functional incompetence and imbalance in the population of T-lymphocytes

2021 ◽  
pp. 109-119
Author(s):  
Н.М. Геворкян ◽  
Н.В. Тишевская
Keyword(s):  
T Lymphocytes ◽  
Personalized Medicine ◽  
The Body ◽  
Lymphoid Cells ◽  
Human Diseases ◽  
Regulatory Role ◽  
Total Rna ◽  
Physiological Processes ◽  
Health And Disease

Цель обзора - анализ клеточной основы патогенеза различных заболеваний в свете регуляторной роли Т-лимфоцитов. Рассматривается роль поликлонального многообразия популяции Т-лимфоцитов, особых свойств этих клеток-представителей гомеостатической системы организма в физиологических процессах в норме и при патологии. Указаны перспективы терапевтического и профилактического воздействий, связанные с использованием суммарных РНК нормальных лимфоидных клеток аллогенной и ксеногенной природы. Указана также возможность создания с помощью лимфоцитарных суммарных РНК адекватных моделей заболеваний человека на пути к развитию персонифицированной медицины. This review provides an analysis of the cellular basis of the pathogenesis of various diseases in the light of the regulatory role of T-lymphocytes. The role of the polyclonal diversity of the population of T-lymphocytes, the special properties of these cells-representatives of the homeostatic system of the body, in physiological processes in health and disease is considered. Prospects for therapeutic and prophylactic effects associated with the use of total RNA of normal lymphoid cells of allogeneic and xenogenic origin are indicated. The possibility of creating, using lymphocytic total RNA, adequate models of human diseases for the development of personalized medicine is also indicated.

The essential role of nesfatin-1 as a biological signal on the body systems

2021 ◽  
pp. 113-118
Keyword(s):  
Metabolic Disorders ◽  
Clinical Medicine ◽  
The Body ◽  
World Population ◽  
Peripheral Tissues ◽  
Future Studies ◽  
Body Organ ◽  
Regulate Food Intake ◽  
System Today

Nesfatin-1is first described in 2006 as an anorectic peptide and regulate food intake. In following years, the studies demonstrated the presence of nesfatin-1 in central and various peripheral tissues. Thus, nesfatin-1 popularity increasing widely in clinical medicine, especially in cardiology, neurology, reproduction, metabolic disorders, psychiatric disorders, gastrointestinal system. Today, the main point concerning nesfatin-1 action in body organ and systems is concentrate its biological signals effects. Thus the increasing knowledge in these area will be highlighted for future studies especially in serious health problem all over the world population.

scholarly journals The Neural Regulation of Cancer

2020 ◽  
Vol 4 (1) ◽  
pp. 371-390
Author(s):  
Shawn Gillespie ◽  
Michelle Monje
Keyword(s):  
Nervous System ◽  
Crucial Role ◽  
The Body ◽  
Tissue Homeostasis ◽  
Neural Regulation ◽  
Physiological Processes

The nervous system is intimately involved in physiological processes from development and growth to tissue homeostasis and repair throughout the body. It logically follows that the nervous system has the potential to play analogous roles in the context of cancer. Progress toward understanding the crucial role of the nervous system in cancer has accelerated in recent years, but much remains to be learned. Here, we highlight rapidly evolving concepts in this burgeoning research space and consider next steps toward understanding and therapeutically targeting the neural regulation of cancer.

scholarly journals The Antiobesity Effects of Centrally Administered Neuromedin U and Neuromedin S Are Mediated Predominantly by the Neuromedin U Receptor 2 (NMUR2)

Endocrinology ◽  
2009 ◽  
Vol 150 (7) ◽  
pp. 3101-3109 ◽  
Author(s):  
Andrea Peier ◽  
Jennifer Kosinski ◽  
Kimberly Cox-York ◽  
Ying Qian ◽  
Kunal Desai ◽  
...  
Keyword(s):  
Food Intake ◽  
Energy Homeostasis ◽  
Central Administration ◽  
Diet Induced Obesity ◽  
Inhibit Food Intake ◽  
Selective Agonists ◽  
Treatment Of Obesity ◽  
The Brain ◽  
Deficient Mice

Neuromedin U (NMU) and neuromedin S (NMS) are structurally related neuropeptides that have been reported to modulate energy homeostasis. Pharmacological data have shown that NMU and NMS inhibit food intake when administered centrally and that NMU increases energy expenditure. Additionally, NMU-deficient mice develop obesity, whereas transgenic mice overexpressing NMU are lean and hypophagic. Two high-affinity NMU/NMS receptors, NMUR1 and NMUR2, have been identified. NMUR1 is predominantly expressed in the periphery, whereas NMUR2 is predominantly expressed in the brain, suggesting that the effects of centrally administered NMU and NMS are mediated by NMUR2. To evaluate the role of NMUR2 in the regulation of energy homeostasis, we characterized NMUR2-deficient (Nmur2−/−) mice. Nmur2−/− mice exhibited a modest resistance to diet-induced obesity that was at least in part due to reduced food intake. Acute central administration of NMU and NMS reduced food intake in wild-type but not in Nmur2−/− mice. The effects on activity and core temperature induced by centrally administered NMU were also absent in Nmur2−/− mice. Moreover, chronic central administration of NMU and NMS evoked significant reductions in body weight and sustained reductions in food intake in mice. In contrast, Nmur2−/− mice were largely resistant to these effects. Collectively, these data demonstrate that the anorectic and weight-reducing actions of centrally administered NMU and NMS are mediated predominantly by NMUR2, suggesting that NMUR2-selective agonists may be useful for the treatment of obesity.

Endocannabinoids and Liver Disease. IV. Endocannabinoid involvement in obesity and hepatic steatosis

2008 ◽  
Vol 294 (5) ◽  
pp. G1101-G1104 ◽  
Author(s):  
George Kunos ◽  
Douglas Osei-Hyiaman
Keyword(s):  
Energy Intake ◽  
Energy Homeostasis ◽  
Biological Effects ◽  
Evolutionarily Conserved ◽  
Multiple Levels ◽  
Treatment Of Obesity ◽  
Limited Physical Activity ◽  
And Storage ◽  
Smoking Marijuana

Endocannabinoids are endogenous lipid mediators that interact with the same receptors as plant-derived cannabinoids to produce similar biological effects. The well-known appetitive effect of smoking marijuana has prompted inquiries into the possible role of endocannabinoids in the control of food intake and body weight. This brief review surveys recent evidence that endocannabinoids and their receptors are involved at multiple levels in the control of energy homeostasis. Endocannabinoids are orexigenic mediators and are part of the leptin-regulated central neural circuitry that controls energy intake. In addition, they act at multiple peripheral sites including adipose tissue, liver, and skeletal muscle to promote lipogenesis and limit fat elimination. Their complex actions could be viewed as anabolic, increasing energy intake and storage and decreasing energy expenditure, as components of an evolutionarily conserved system that has insured survival under conditions of starvation. In the era of plentiful food and limited physical activity, pharmacological inhibition of endocannabinoid activity offers benefits in the treatment of obesity and its hormonal/metabolic consequences.

scholarly journals MicroRNAs as Important Regulators Mediate the Multiple Differentiation of Mesenchymal Stromal Cells

2021 ◽  
Vol 9 ◽  
Author(s):  
Chao Yang ◽  
Maowen Luo ◽  
Yu Chen ◽  
Min You ◽  
Qiang Chen
Keyword(s):  
Regenerative Medicine ◽  
Stromal Cells ◽  
Critical Role ◽  
The Body ◽  
Disease Treatment ◽  
Multipotent Stem Cells ◽  
Physiological Processes ◽  
Multiple Differentiation ◽  
Differentiation Efficiency

MicroRNAs (miRNAs) are endogenous short non-encoding RNAs which play a critical role on the output of the proteins, and influence multiple biological characteristics of the cells and physiological processes in the body. Mesenchymal stem/stromal cells (MSCs) are adult multipotent stem cells and characterized by self-renewal and multidifferentiation and have been widely used for disease treatment and regenerative medicine. Meanwhile, MSCs play a critical role in maintaining homeostasis in the body, and dysfunction of MSC differentiation leads to many diseases. The differentiation of MSCs is a complex physiological process and is the result of programmed expression of a series of genes. It has been extensively proven that the differentiation process or programmed gene expression is also regulated accurately by miRNAs. The differentiation of MSCs regulated by miRNAs is also a complex, interdependent, and dynamic process, and a full understanding of the role of miRNAs will provide clues on the appropriate upregulation or downregulation of corresponding miRNAs to mediate the differentiation efficiency. This review summarizes the roles and associated signaling pathways of miRNAs in adipogenesis, chondrogenesis, and osteogenesis of MSCs, which may provide new hints on MSCs or miRNAs as therapeutic strategies for regenerative medicine and biotherapy for related diseases.

scholarly journals Role of N-Linked Glycosylation in PKR2 Trafficking and Signaling

2021 ◽  
Vol 15 ◽  
Author(s):  
Jissele A. Verdinez ◽  
Julien A. Sebag
Keyword(s):  
Plasma Membrane ◽  
Energy Homeostasis ◽  
Reproductive Function ◽  
Receptor Trafficking ◽  
Membrane Localization ◽  
Accessory Protein ◽  
Post Translational Modification ◽  
Physiological Processes ◽  
Glycosylation Sites

Prokineticin receptors are GPCRs involved in several physiological processes including the regulation of energy homeostasis, nociception, and reproductive function. PKRs are inhibited by the endogenous accessory protein MRAP2 which prevents them from trafficking to the plasma membrane. Very little is known about the importance of post-translational modification of PKRs and their role in receptor trafficking and signaling. Here we identify 2 N-linked glycosylation sites within the N-terminal region of PKR2 and demonstrate that glycosylation of PKR2 at position 27 is important for its plasma membrane localization and signaling. Additionally, we show that glycosylation at position 7 results in a decrease in PKR2 signaling through Gαs without impairing Gαq/11 signaling.

PDIA3 Reduce Glioma-associated Macrophage/microglia Pro-tumor Activation trough IL-6-STAT3-PDIA3 Pathway.

2020 ◽  
Author(s):  
Marta Chiavari ◽  
Gabriella Maria Pia Ciotti ◽  
Francesco Canonico ◽  
Fabio Altieri ◽  
Pierluigi Navarra ◽  
...  
Keyword(s):  
Overall Survival ◽  
Endoplasmic Reticulum ◽  
The Cancer Genome Atlas ◽  
Main Function ◽  
Physiological Processes ◽  
Relevant Role ◽  
Cancer Genome Atlas ◽  
Thiol Oxidoreductase

Abstract Background: Glioblastoma (GB - grade IV glioma) is the most aggressive and common cancer of central nervous system with an overall survival of 14-16 months. The GB tumor microenvironment includes cells of the innate immune system identified as glioma-associated microglia/macrophages (GAMs). It is known that between GAMs and GB cells there is a double interaction, but the role of GAMs is still poorly characterized. The endoplasmic reticulum (ER) protein ERp57, also known as PDIA3, is a thiol oxidoreductase with main function related on glycoprotein folding in endoplasmic reticulum. However, PDIA3 shows different functions. In fact, the various subcellular localizations and binding partners of PDIA3 affect numerous physiological processes and diseases: different regulation and modulation of PDIA3 has been reported in multiple pathologies including neurodegenerative diseases and cancer. Methods: In the present work, we evaluated in both GB cells and microglia-macrophage cells the expression of PDIA3 using specimens collected after surgical from 18 GB patients. In addition, we studied in vitro microglia-glioma interaction to determine the role of PDIA3 in viability and the activation of both GB and microglia cells. The study was carried using PDIA3-silenced T98G cells and/or using a pharmacological inhibitor of PDIA3 activity (Punicalagin-PUN).Results: We initially investigated the role of the PDIA3 in GB survival by inquiring The Cancer Genome Atlas dataset. The results indicated that 352 out of 690 patients reported over-expression of PDIA3, which significantly correlated with a ~55% reduction of overall survival. Subsequently, for the first time, we investigated the PDIA3 expression in the tumor and the nearby parenchyma of 18 GB patients and our data showed a significant upregulation (15% vs 10%) of ERp57/PDIA3 in GAMs of tumor specimens respect the microglia present in parenchyma. In addition, we show that conditioned medium (CMs) obtained from both wild type T98G and PDIA3 silenced T98G induced an activation of microglia cells, but the PDIA3 silenced-T98G CMs significant limited the microglia pro-tumor activation probably through a IL-6-STAT3-PDIA3 dependent mechanism. Conclusion: Our data support the relevant role of PDIA3 expression in GB pathology and link the different activation of microglia to a mechanism a IL-6-STAT3-PDIA3 dependent.

scholarly journals Role of Carbonic Anhydrases and Inhibitors in Acid–Base Physiology: Insights from Mathematical Modeling

2019 ◽  
Vol 20 (15) ◽  
pp. 3841 ◽  
Author(s):  
Occhipinti ◽  
Boron
Keyword(s):  
Mathematical Modeling ◽  
Ph Regulation ◽  
Reaction Diffusion ◽  
The Body ◽  
Whole Body ◽  
Facilitated Diffusion ◽  
Carbonic Anhydrases ◽  
Physiological Processes ◽  
Urinary Acid

Carbonic anhydrases (CAs) catalyze a reaction fundamental for life: the bidirectional conversion of carbon dioxide (CO2) and water (H2O) into bicarbonate (HCO3−) and protons (H+). These enzymes impact numerous physiological processes that occur within and across the many compartments in the body. Within compartments, CAs promote rapid H+ buffering and thus the stability of pH-sensitive processes. Between compartments, CAs promote movements of H+, CO2, HCO3−, and related species. This traffic is central to respiration, digestion, and whole-body/cellular pH regulation. Here, we focus on the role of mathematical modeling in understanding how CA enhances buffering as well as gradients that drive fluxes of CO2 and other solutes (facilitated diffusion). We also examine urinary acid secretion and the carriage of CO2 by the respiratory system. We propose that the broad physiological impact of CAs stem from three fundamental actions: promoting H+ buffering, enhancing H+ exchange between buffer systems, and facilitating diffusion. Mathematical modeling can be a powerful tool for: (1) clarifying the complex interdependencies among reaction, diffusion, and protein-mediated components of physiological processes; (2) formulating hypotheses and making predictions to be tested in wet-lab experiments; and (3) inferring data that are impossible to measure.

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