Endogenous NUCB2/Nesfatin-1 Regulates Energy Homeostasis Under Physiological Conditions in Male Rats

2020 ◽  
Vol 52 (09) ◽  
pp. 676-684
Author(s):  
Anna-Maria Wilz ◽  
Kerstin Wernecke ◽  
Lena Appel ◽  
Johanna Kahrs ◽  
Riccardo Dore ◽  
...  
Keyword(s):  
Paraventricular Nucleus ◽  
Calcium Binding ◽  
Energy Homeostasis ◽  
Physiological Role ◽  
Male Rats ◽  
Peripheral Tissues ◽  
Downstream Target ◽  
Food And Water Intake ◽  
Pharmacological Blockade

AbstractNesfatin-1 is the proteolytic cleavage product of Nucleobindin 2, which is expressed both in a number of brain nuclei (e. g., the paraventricular nucleus of the hypothalamus) and peripheral tissues. While Nucleobindin 2 acts as a calcium binding protein, nesfatin-1 was shown to affect energy homeostasis upon central nervous administration by decreasing food intake and increasing thermogenesis. In turn, Nucleobindin 2 mRNA expression is downregulated in starvation and upregulated in the satiated state. Still, knowledge about the physiological role of endogenous Nucleobindin 2/nesfatin-1 in the control of energy homeostasis is limited and since its receptor has not yet been identified, rendering pharmacological blockade impossible. To overcome this obstacle, we tested and successfully established an antibody-based experimental model to antagonize the action of nesfatin-1. This model was then employed to investigate the physiological role of endogenous Nucleobindin 2/nesfatin-1. To this end, we applied nesfatin-1 antibody into the paraventricular nucleus of satiated rats to antagonize the presumably high endogenous Nucleobindin 2/nesfatin-1 levels in this feeding condition. In these animals, nesfatin-1 antibody administration led to a significant decrease in thermogenesis, demonstrating the important role of endogenous Nucleobindin 2/nesfatin-1in the regulation of energy expenditure. Additionally, food and water intake were significantly increased, confirming and complementing previous findings. Moreover, neuropeptide Y was identified as a major downstream target of endogenous Nucleobindin 2/nesfatin-1.

scholarly journals Exercise-Induced Circulating Irisin Level Is Correlated with Improved Cardiac Function in Rats

2020 ◽  
Vol 17 (11) ◽  
pp. 3863 ◽  
Author(s):  
Dae Yun Seo ◽  
Jun Hyun Bae ◽  
Tae Nyun Kim ◽  
Hyo-Bum Kwak ◽  
Pham Trong Kha ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Energy Homeostasis ◽  
Physiological Role ◽  
Male Rats ◽  
Sprague Dawley ◽  
Epididymal Fat ◽  
Abdominal Visceral Fat ◽  
Exercise Induced ◽  
Fractional Shortening

Irisin, a recently identified myokine, plays an important physiological role in modulating energy homeostasis. However, the role of irisin in cardiac function during exercise has not been evaluated. In this study, we investigated the effect of exercise on irisin, pro-inflammatory cytokines, and cardiac function during 12 weeks of exercise in rats. Eight-week-old Sprague-Dawley male rats were randomly divided into two groups (n = 9 per group): sedentary control (CON) and exercise (EXE) groups. The EXE group was trained on a motorized treadmill at 20 m/min, for 60 min/day, five times/week for 12 weeks. The EXE group showed a decrease in abdominal visceral fat (p < 0.05), epididymal fat (p < 0.01), and total cholesterol (TC) (p < 0.05) and an increase in irisin levels (p < 0.01). Irisin negatively correlated with abdominal visceral (p < 0.05) and epididymal fat (p < 0.05) and positively correlated with the ejection fraction (p < 0.05), fractional shortening (p < 0.05), and cardiac output (p < 0.05). In conclusion, exercise decreases the abdominal visceral and epididymal fat and TC levels, possibly caused by elevated irisin levels, thus improving the cardiac function. This suggests that exercise-induced circulating irisin levels correlate with improved cardiac function in rats.

scholarly journals Az ösztrogénmetabolom biológiai és klinikai jelentősége lokális folyamatokban

2017 ◽  
Vol 158 (24) ◽  
pp. 929-937
Author(s):  
Krisztián Kovács ◽  
Barna Vásárhelyi ◽  
Katalin Mészáros ◽  
Attila Patócs ◽  
Gellért Karvaly
Keyword(s):  
Biological Activity ◽  
Clinical Significance ◽  
Physiological Role ◽  
Tissue Homeostasis ◽  
Diagnostic Significance ◽  
Peripheral Tissues ◽  
Breakdown Process ◽  
Specific Manner ◽  
Related Compounds

Abstract: Considerable knowledge has been gathered on the physiological role of estrogens. However, fairly little information is available on the role of compounds produced in the breakdown process of estrone and estradiol wich may play a role in various diseases associated with estrogen impact. To date, approximately 15 extragonadal estrogen-related compounds have been identified. These metabolites may exert protective, or, instead, pro-inflammatory and/or pro-oncogenic activity in a tissue-specific manner. Systemic and local estrogen metabolite levels are not necesserily correlated, which may promote the diagnostic significance of the locally produced estrogen metabolites in the future. The aim of the present study is a bibliographic review of the extragonadal metabolome in peripheral tissues, and to highlight the role of the peripheral tissue homeostasis of estrogens as well as the non-hormonal biological activity and clinical significance of the estrogen metabolome. Orv Hetil. 2017; 158(24): 929–937.

scholarly journals PECULIARITIES OF IONOREGULATORY RENAL FUNCTION OF RATS IN THE DYNAMICS OF EXPERIMENTAL DIABETES MELLITUS DEVELOPMENT WITH UNDERLYING PHARMACOLOGICAL BLOCADE OF RENIN-ANGIOTENSINALDOSTERONE SYSTEM

2021 ◽  
Vol 19 (4) ◽  
Author(s):  
О.А. Olenovych
Keyword(s):  
Diabetes Mellitus ◽  
Renal Function ◽  
Free Water ◽  
Distal Segment ◽  
Male Rats ◽  
Sodium Reabsorption ◽  
Free Water Clearance ◽  
Glomerular Filtrate ◽  
Pharmacological Blockade

The aim of the study – to explore the role of the renin-angiotensin-aldosteronesystem (RAAS) in the disturbance of ionoregulatory renal function in alloxan-inducedexperimental diabetes mellitus (EDM).Material and methods. The experiments were carried out on 78 white non-linearmature male rats with 11-, 26- and 46-day long alloxan-induced EDM with underlyingpharmacological blockade of RAAS by administration of kaptopril. The study ofionoregulating function of the kidneys was provided by the clearance method under thecondition of water 2-hour diuresis.Results. Pharmacological blockade of RAAS in rats with alloxan-induced EDM causedan intensification of natriuresis at all stages of the experiment: increased urinaryconcentration of sodium ions, its excretion and clearance. On the 11th day of EDM, thesodium filtration charge increased with the development of hyponatremia, proximal anddistal sodium reabsorption standardized in volume of glomerular filtrate (GF) decreased,kaliuresis was suppressed, and sodium-free water clearance elevated. In case of 26-daylong EDM, the sodium filtration charge decreased, its absolute and relative reabsorption,the distal sodium reabsorption standardized by GF increased. Kaliuresis increased. In46-day long EDM, the sodium filtration charge decreased, and hyponatremia enhanced.Absolute and relative sodium reabsorption reduced due to both – proximal and distal.Kaliuresis augmented, the clearance of sodium-free water declined.Conclusions. The increase in urinary sodium loss during the 11-day EDM is stipulatedby glomerular hyperfiltration, causing a functional weakening of the tubulotubularbalance and relative dysfunction of the distal segment of the nephron, emphasizing therenoprotective effect of RAAS on ionoregulatory function of the kidneys. The decrease inthe total reabsorption potential of the tubular segment of the nephron in the dynamics ofEDM development reflects on the proximal tubules, and preserved tubulotubular balancecertifies functional intactness of the distal tubules in 26-day long EDM. RAAS pathologicalactivation and attenuation of the renal blood flow autoregulation by tubuloglomerularfeedback may serve as an initiating factor in the development of tubular disorders in 26-day long alloxan diabetes with following progression in 46-day long EDM.

scholarly journals LGR4 and Its Ligands, R-Spondin 1 and R-Spondin 3, Regulate Food Intake in the Hypothalamus of Male Rats

Endocrinology ◽  
2014 ◽  
Vol 155 (2) ◽  
pp. 429-440 ◽  
Author(s):  
Ji-Yao Li ◽  
Biaoxin Chai ◽  
Weizhen Zhang ◽  
Danielle M. Fritze ◽  
Chao Zhang ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Food Intake ◽  
Neuropeptide Y ◽  
Paraventricular Nucleus ◽  
Median Eminence ◽  
Energy Homeostasis ◽  
Male Rats ◽  
The Third ◽  
The Brain

The hypothalamus plays a key role in the regulation of feeding behavior. Several hypothalamic nuclei, including the arcuate nucleus (ARC), paraventricular nucleus, and ventromedial nucleus of the hypothalamus (VMH), are involved in energy homeostasis. Analysis of microarray data derived from ARC revealed that leucine-rich repeat-containing G protein-coupled receptor 4 (LGR4) is highly expressed. LGR4, LGR5, and LGR6 form a subfamily of closely related receptors. Recently, R-spondin (Rspo) family proteins were identified as ligands of the LGR4 subfamily. In the present study, we investigated the distribution and function of LGR4–LGR6 and Rspos (1–4) in the brain of male rat. In situ hybridization showed that LGR4 is expressed in the ARC, VMH, and median eminence of the hypothalamus. LGR4 colocalizes with neuropeptide Y, proopiomelanocortin, and brain-derived neurotrophic factor neurons. LGR5 is not detectable with in situ hybridization; LGR6 is only expressed in the epithelial lining of the lower portion of the third ventricle and median eminence. Rspo1 is expressed in the VMH and down-regulated with fasting. Rspo3 is expressed in the paraventricular nucleus and also down-regulated with fasting. Rspos 1 and 3 colocalize with the neuronal marker HuD, indicating that they are expressed by neurons. Injection of Rspo1 or Rspo3 into the third brain ventricle inhibited food intake. Rspo1 decreased neuropeptide Y and increased proopiomelanocortin expression in the ARC. Rspo1 and Rspo3 mRNA is up-regulated by insulin. These data indicate that Rspo1 and Rspo3 and their receptor LGR4 form novel circuits in the brain to regulate energy homeostasis.

Tissue distribution of rat S100 alpha and S100 beta and S100-binding proteins

1987 ◽  
Vol 252 (3) ◽  
pp. C285-C289 ◽  
Author(s):  
D. B. Zimmer ◽  
L. J. Van Eldik
Keyword(s):  
Calcium Binding ◽  
Binding Proteins ◽  
Physiological Role ◽  
Rat Tissues ◽  
Differential Distribution ◽  
Binding Profile ◽  
Calmodulin Binding ◽  
The Individual ◽  
Intracellular Targets

To understand the physiological role of the calcium-binding proteins S100 alpha and S100 beta, it is necessary to determine the distribution of these proteins and detect their intracellular targets in various tissues. The distribution of immunoreactive S100 alpha and S100 beta in various rat tissues was examined by radioimmunoassay. All tissues examined contained detectable S100, but the S100 beta/S100 alpha ratio in each tissue differed. Brain, adipose, and testes contained 18- to 40-fold more S100 beta than S100 alpha; skin and liver contained approximately equivalent amounts and kidney, spleen, and heart contained 8- to 75-fold more S100 alpha than S100 beta. Analysis of S100-binding proteins by gel overlay showed that each tissue possessed its own complement of binding proteins. The S100 beta-binding profile was indistinguishable from the S100 alpha-binding profile and both of these profiles were distinct from the calmodulin-binding profile. These observations suggest that the differential distribution and quantity of the individual S100 polypeptides and their binding proteins in various tissues may be important factors in determining S100 function.

scholarly journals Annexins and their role in the control of symbioses development of plants with nitrogen-fixing bacteria and arbuscular mycorrhizal fungi

2020 ◽  
Author(s):  
Elena Anatolyevna Dolgikh ◽  
Darya Vladimirovna Kustova
Keyword(s):  
Mycorrhizal Fungi ◽  
Calcium Binding ◽  
Structural Organization ◽  
Physiological Role ◽  
Arbuscular Mycorrhizal ◽  
Structural Similarity ◽  
Binding Motifs ◽  
Calcium Dependent ◽  
Cellular Processes

Annexins belong to the superfamily of calcium-dependent phospholipid binding proteins. The participation of these proteins in the regulation of structural organization of membranes, vesicular transport and a variety of signal transduction pathways is important for many cellular processes. Despite the structural similarity with animal annexins, plant annexins are characterized by significant variability of the N-terminal region and modification of calcium-binding motifs in II and III repeats, while calcium-binding motifs in I and IV repetitions remain conservative. However, the physiological role of animal and plant annexins, as well as mechanisms of their influence on calcium metabolism, may be similar. This review focused on the latest data about the structure and functioning of plant annexins.

scholarly journals Emerging Role of l-Dopa Decarboxylase in Flaviviridae Virus Infections

Cells ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 837 ◽  
Author(s):  
Frakolaki ◽  
Kalliampakou ◽  
Kaimou ◽  
Moraiti ◽  
Kolaitis ◽  
...  
Keyword(s):  
Viral Replication ◽  
Viral Infections ◽  
Physiological Role ◽  
Inverse Correlation ◽  
Dopa Decarboxylase ◽  
Hcv Rna ◽  
Virus Infections ◽  
Peripheral Tissues ◽  
Functional Complex

l-dopa decarboxylase (DDC) that catalyzes the biosynthesis of bioactive amines, such as dopamine and serotonin, is expressed in the nervous system and peripheral tissues, including the liver, where its physiological role remains unknown. Recently, we reported a physical and functional interaction of DDC with the major signaling regulator phosphoinosite-3-kinase (PI3K). Here, we provide compelling evidence for the involvement of DDC in viral infections. Studying dengue (DENV) and hepatitis C (HCV) virus infection in hepatocytes and HCV replication in liver samples of infected patients, we observed a negative association between DDC and viral replication. Specifically, replication of both viruses reduced the levels of DDC mRNA and the ~120 kDa SDS-resistant DDC immunoreactive functional complex, concomitant with a PI3K-dependent accumulation of the ~50 kDa DDC monomer. Moreover, viral infection inhibited PI3K-DDC association, while DDC did not colocalize with viral replication sites. DDC overexpression suppressed DENV and HCV RNA replication, while DDC enzymatic inhibition enhanced viral replication and infectivity and affected DENV-induced cell death. Consistently, we observed an inverse correlation between DDC mRNA and HCV RNA levels in liver biopsies from chronically infected patients. These data reveal a novel relationship between DDC and Flaviviridae replication cycle and the role of PI3K in this process.

scholarly journals Importance of the Paraventricular Nucleus of the Hypothalamus as a Component of a Neural Pathway between the Brain and the Testes that Modulates Testosterone Secretion Independently of the Pituitary

Endocrinology ◽  
2003 ◽  
Vol 144 (2) ◽  
pp. 594-598 ◽  
Author(s):  
Daniel J. Selvage ◽  
Catherine Rivier
Keyword(s):  
Paraventricular Nucleus ◽  
Leydig Cell ◽  
Pseudorabies Virus ◽  
Cell Function ◽  
Brain Area ◽  
Male Rats ◽  
Neural Pathway ◽  
Electrolytic Lesions ◽  
The Brain

We previously reported that in adult male rats, the intracerebroventricular (icv) injection of corticotropin-releasing factor (CRF) or the β-adrenergic agonist isoproterenol (ISO) significantly inhibited the ability of human chorionic gonadotropin (hCG) to stimulate testosterone (T) secretion. The finding that this phenomenon also took place when LH release had been blocked with an LHRH antagonist suggested that icv CRF and ISO did not alter Leydig cell function by influencing the activity of pituitary gonadotrophs. We therefore proposed the existence of a neural pathway connecting the brain to the testes, whose activation by icv CRF or ISO interfered with T secretion. Based on the intratesticular injection of the transganglionic tracer pseudorabies virus, we recently identified the paraventricular nucleus (PVN) of the hypothalamus as a component of this neural link. The aim of the present work was to investigate the functional role of this brain area in mediating the ability of CRF and ISO to inhibit the ability of hCG to stimulate T secretion. We first demonstrated that local microinfusion of CRF or ISO directly into the PVN mimicked the effect of their icv injection, suggesting that the PVN does indeed represent a site of action of ISO and CRF in altering Leydig cell responsiveness to gonadotropin. In contrast, neither CRF nor ISO microinfusion into the central amygdala or the frontal cortex influenced hCG-stimulated T secretion. To further investigate the role of the PVN in ISO- and CRF-induced blunting of hCG stimulation of T, we determined the effect of icv CRF or ISO on testicular activity of rats with electrolytic lesions of the PVN. These lesions, which did not in themselves influence Leydig cell responsiveness to hCG, blocked the effect of both icv ISO and CRF on hCG-induced T release. Collectively, these results support the hypothesis that CRF- and ISO-induced activation of cells in the area of the PVN decreases the ability of gonadotropin to release T and suggests that this nucleus represents an important site of the proposed neural connection between the brain and the testes.

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