scholarly journals Broadening the role of osteocalcin in hypothalamic-pituitary-gonadal axis

2021 ◽  
Author(s):  
Chang Shan ◽  
Jiang Yue ◽  
Wei Liu
Keyword(s):  
Developmental Disorders ◽  
Active Form ◽  
Peripheral Tissues ◽  
Glucose And Lipid Metabolism ◽  
Reproductive Endocrine ◽  
The Central Nervous System ◽  
Testosterone Biosynthesis ◽  
Increase Insulin Secretion ◽  
Functional Mechanisms

Bone is emerging as a versatile endocrine organ and its interactions with apparently unrelated organs are being more widely recognized. Osteocalcin (OCN), a polypeptide hormone secreted by osteoblasts, has been found to exert multiple endocrine functions through its metabolically active form, uncarboxylated OCN (uOCN). Mounting evidence has shown that following its binding to G-protein coupled receptor 6a (Gprc6a) in the peripheral tissues, uOCN acts on pancreatic β cells to increase insulin secretion, and on muscle and white adipose tissue to promote glucose and lipid metabolism. More strikingly, researchers have found a surprising role of uOCN in testicular function to facilitating testosterone biosynthesis and regulating male fertility via a pancreas-bone-gonadal axis. However, the detailed functional mechanisms of uOCN on the hypothalamic-pituitary-gonadal axis or the pancreas-bone-gonadal axis are not fully understood. Besides highlighting the regulatory mechanisms of uOCN in the central nervous system, hypothalamus and pituitary, we also discuss its role in male as well as female fertility and its potential clinical implications in some reproductive endocrine diseases and pubertal developmental disorders.

scholarly journals The Role of Morphine in Animal Models of Human Cancer: Does Morphine Promote or Inhibit the Tumor Growth?

2013 ◽  
Vol 2013 ◽  
pp. 1-4 ◽  
Author(s):  
Sabrina Bimonte ◽  
Antonio Barbieri ◽  
Giuseppe Palma ◽  
Claudio Arra
Keyword(s):  
Tumor Growth ◽  
Human Cancer ◽  
Primary Tumour ◽  
Cancer Cell Growth ◽  
Peripheral Tissues ◽  
Patients With Cancer ◽  
Relieve Pain ◽  
Pain And Suffering ◽  
The Central Nervous System

Morphine, a highly potent analgesic agent, is widely used to relieve pain and suffering of patients with cancer. Additionally, it has been reported that morphine is important in the regulation of cancerous tissue. Morphine relieves pain by acting directly on the central nervous system, although its activities on peripheral tissues are responsible for many adverse side effects. For these reasons, it is very important also to understand the role of morphine in cancer treatment. The published literature reporting the effect of morphine on tumor growth presents some discrepancies, with reports suggesting that morphine may either promote or inhibit the tumor growth. It has been also demonstrated that morphine modulates angiogenesis which is important for primary tumour growth, invasiveness, and the development of metastasis. This review will focus on the latest findings on the role of morphine in the regulation of cancer cell growth and angiogenesis.

scholarly journals The Biosynthesis, Signaling, and Neurological Functions of Bile Acids

Biomolecules ◽  
2019 ◽  
Vol 9 (6) ◽  
pp. 232 ◽  
Author(s):  
Yoshimitsu Kiriyama ◽  
Hiromi Nochi
Keyword(s):  
Bile Acids ◽  
Muscarinic Acetylcholine Receptor ◽  
Dietary Lipids ◽  
Farnesoid X Receptor ◽  
Na Channel ◽  
Peripheral Tissues ◽  
Surface Receptors ◽  
Glucose And Lipid Metabolism ◽  
Protein Receptor ◽  
The Central Nervous System

Bile acids (BA) are amphipathic steroid acids synthesized from cholesterol in the liver. They act as detergents to expedite the digestion and absorption of dietary lipids and lipophilic vitamins. BA are also considered to be signaling molecules, being ligands of nuclear and cell-surface receptors, including farnesoid X receptor and Takeda G-protein receptor 5. Moreover, BA also activate ion channels, including the bile acid-sensitive ion channel and epithelial Na+ channel. BA regulate glucose and lipid metabolism by activating these receptors in peripheral tissues, such as the liver and brown and white adipose tissue. Recently, 20 different BA have been identified in the central nervous system. Furthermore, BA affect the function of neurotransmitter receptors, such as the muscarinic acetylcholine receptor and γ-aminobutyric acid receptor. BA are also known to be protective against neurodegeneration. Here, we review recent findings regarding the biosynthesis, signaling, and neurological functions of BA.

scholarly journals Stroke in SARS-CoV-2 Infection: A Pictorial Overview of the Pathoetiology

2021 ◽  
Vol 8 ◽  
Author(s):  
Saeideh Aghayari Sheikh Neshin ◽  
Shima Shahjouei ◽  
Eric Koza ◽  
Isabel Friedenberg ◽  
Faezeh Khodadadi ◽  
...  
Keyword(s):  
Inflammatory Cytokine ◽  
Renin Angiotensin System ◽  
Cardiovascular Complications ◽  
Elevated Risk ◽  
Peripheral Tissues ◽  
Angiotensin System ◽  
Cerebrovascular Complications ◽  
The Central Nervous System ◽  
Personalized Approach

Since the early days of the pandemic, there have been several reports of cerebrovascular complications during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Numerous studies proposed a role for SARS-CoV-2 in igniting stroke. In this review, we focused on the pathoetiology of stroke among the infected patients. We pictured the results of the SARS-CoV-2 invasion to the central nervous system (CNS) via neuronal and hematogenous routes, in addition to viral infection in peripheral tissues with extensive crosstalk with the CNS. SARS-CoV-2 infection results in pro-inflammatory cytokine and chemokine release and activation of the immune system, COVID-19-associated coagulopathy, endotheliitis and vasculitis, hypoxia, imbalance in the renin-angiotensin system, and cardiovascular complications that all may lead to the incidence of stroke. Critically ill patients, those with pre-existing comorbidities and patients taking certain medications, such as drugs with elevated risk for arrhythmia or thrombophilia, are more susceptible to a stroke after SARS-CoV-2 infection. By providing a pictorial narrative review, we illustrated these associations in detail to broaden the scope of our understanding of stroke in SARS-CoV-2-infected patients. We also discussed the role of antiplatelets and anticoagulants for stroke prevention and the need for a personalized approach among patients with SARS-CoV-2 infection.

scholarly journals ANGPTL8 in metabolic homeostasis: more friend than foe?

Open Biology ◽  
2021 ◽  
Vol 11 (9) ◽  
Author(s):  
Chang Guo ◽  
Chenxi Wang ◽  
Xia Deng ◽  
Jianqiang He ◽  
Ling Yang ◽  
...  
Keyword(s):  
Metabolic Disorders ◽  
Metabolic Diseases ◽  
Hepatic Glucose Production ◽  
Physiological Role ◽  
Glucose Production ◽  
Peripheral Tissues ◽  
Glucose And Lipid Metabolism ◽  
Hepatic Glucose

ANGPTL8 is an important cytokine, which is significantly increased in type 2 diabetes mellitus (T2DM), obesity and metabolic syndrome. Many studies have shown that ANGPTL8 can be used as a bio-marker of these metabolic disorders related diseases, and the baseline ANGPTL8 level has also been found to be positively correlated with retinopathy and all-cause mortality in patients with T2DM. This may be related to the inhibition of lipoprotein lipase activity and the reduction of circulating triglyceride (TG) clearance by ANGPTL8. Consistently, inhibition of ANGPTL8 seems to prevent or improve atherosclerosis. However, it is puzzling that ANGPTL8 seems to have a directing function for TG uptake in peripheral tissues; that is, ANGPTL8 specifically enhances the reserve and buffering function of white adipose tissue, which may alleviate the ectopic lipid accumulation to a certain extent. Furthermore, ANGPTL8 can improve insulin sensitivity and inhibit hepatic glucose production. These contradictory results lead to different opinions on the role of ANGPTL8 in metabolic disorders. In this paper, the correlation between ANGPTL8 and metabolic diseases, the regulation of ANGPTL8 and the physiological role of ANGPTL8 in the process of glucose and lipid metabolism were summarized, and the physiological/pathological significance of ANGPTL8 in the process of metabolic disorder was discussed.

scholarly journals Monoamine Oxidase-Related Vascular Oxidative Stress in Diseases Associated with Inflammatory Burden

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Adrian Sturza ◽  
Călin M. Popoiu ◽  
Mihaela Ionică ◽  
Oana M. Duicu ◽  
Sorin Olariu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Brain Diseases ◽  
Noncommunicable Diseases ◽  
Peripheral Tissues ◽  
The Central Nervous System ◽  
Available Information ◽  
New Generation ◽  
Vascular Oxidative Stress ◽  
Inflammatory Burden

Monoamine oxidases (MAO) with 2 isoforms, A and B, located at the outer mitochondrial membrane are flavoenzyme membranes with a major role in the metabolism of monoaminergic neurotransmitters and biogenic amines in the central nervous system and peripheral tissues, respectively. In the process of oxidative deamination, aldehydes, hydrogen peroxide, and ammonia are constantly generated as potential deleterious by-products. While being systematically studied for decades as sources of reactive oxygen species in brain diseases, compelling evidence nowadays supports the role of MAO-related oxidative stress in cardiovascular and metabolic pathologies. Indeed, oxidative stress and chronic inflammation are the most common pathomechanisms of the main noncommunicable diseases of our century. MAO inhibition with the new generation of reversible and selective drugs has recently emerged as a pharmacological strategy aimed at mitigating both processes. The aim of this minireview is to summarize available information regarding the contribution of MAO to the vascular oxidative stress and endothelial dysfunction in hypertension, metabolic disorders, and chronic kidney disease, all conditions associated with increased inflammatory burden.

scholarly journals Tissue-Specific Effects of Leptin on Glucose and Lipid Metabolism

2020 ◽  
Author(s):  
Sandra Pereira ◽  
Daemon L Cline ◽  
Maria M Glavas ◽  
Scott D Covey ◽  
Timothy J Kieffer
Keyword(s):  
Body Weight ◽  
Therapeutic Potential ◽  
Peripheral Tissues ◽  
Glucose Lowering ◽  
Glucose And Lipid Metabolism ◽  
Specific Effects ◽  
Regulate Body Weight ◽  
Activation Status

Abstract The discovery of leptin was intrinsically associated with its ability to regulate body weight. However, the effects of leptin are more far-reaching and include profound glucose-lowering and anti-lipogenic effects, independent of leptin’s regulation of body weight. Regulation of glucose metabolism by leptin is mediated both centrally and via peripheral tissues and is influenced by the activation status of insulin signaling pathways. Ectopic fat accumulation is diminished by both central and peripheral leptin, an effect that is beneficial in obesity-associated disorders. The magnitude of leptin action depends upon the tissue, sex, and context being examined. Peripheral tissues that are of particular relevance include the endocrine pancreas, liver, skeletal muscle, adipose tissues, immune cells, and the cardiovascular system. As a result of its potent metabolic activity, leptin is used to control hyperglycemia in patients with lipodystrophy and is being explored as an adjunct to insulin in patients with type 1 diabetes. To fully understand the role of leptin in physiology and to maximize its therapeutic potential, the mechanisms of leptin action in these tissues needs to be further explored.

scholarly journals Peripheral Spexin Inhibited Food Intake in Mice

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Shuangyu Lv ◽  
Yuchen Zhou ◽  
Yu Feng ◽  
Xiaomei Zhang ◽  
Xinyue Wang ◽  
...  
Keyword(s):  
Food Intake ◽  
Dark Period ◽  
Mrna Level ◽  
Inhibitory Effect ◽  
Appetite Regulation ◽  
Peripheral Tissues ◽  
Anorectic Effect ◽  
The Central Nervous System ◽  
Cumulative Food Intake

Spexin (SPX, NPQ), a novel endogenous neuropeptide, was firstly identified by bioinformatics. Spexin gene and protein widely distributed in the central nervous system and peripheral tissues, such as the hypothalamus and digestive tract. The role of spexin in appetite regulation in mammalian is still unclear. The present study was designed to investigate the mechanism and effect of peripheral spexin on food intake in mice. During the light period, an intraperitoneal (i.p.) injection of spexin (10 nmol/mouse) significantly inhibited cumulative food intake at 2, 4, and 6 h after treatment in fasted mice. During the dark period, spexin (1 and 10 nmol/mouse, i.p.) significantly suppressed cumulative food intake at 4 and 6 h after treatment in freely feeding mice. The GALR3 antagonist SNAP37889, not GALR2 antagonist, significantly antagonized the inhibitory effect on cumulative food intake (0–6 h) induced by spexin. Spexin significantly reduced the mRNA level of Npy mRNA, not Agrp, Pomc, Cart, Crh, Orexin, or Mch, in the hypothalamus. Spexin (10 nmol/mouse, i.p.) increased the number of c-Fos positive neurons in hypothalamic AHA and SCN, but not in ARC, DMN, LHA, PVN, SON, or VMH. The hypothalamic p-CaMK2 protein expression was upregulated by spexin. This study indicated that acute peripheral injection of spexin inhibited mouse food intake. The anorectic effect may be mediated by GALR3, and inhibiting neuropeptide Y (NPY) via p-CaMK2 and c-Fos in the hypothalamus.

The Neurokinins: Peptidomimetic Ligand Design and Therapeutic Applications

2020 ◽  
Vol 27 (9) ◽  
pp. 1515-1561 ◽  
Author(s):  
Charlène Gadais ◽  
Steven Ballet
Keyword(s):  
Peripheral Tissues ◽  
Neurokinin Receptors ◽  
Conformational Constraints ◽  
Wide Range ◽  
Agonist And Antagonist ◽  
Nk1 Antagonist ◽  
The Central Nervous System ◽  
Food Drug Administration ◽  
Post Operative Nausea

The neurokinins are indisputably essential neurotransmitters in numerous pathoand physiological events. Being widely distributed in the Central Nervous System (CNS) and peripheral tissues, their discovery rapidly promoted them to drugs targets. As a necessity for molecular tools to understand the biological role of this class, endogenous peptides and their receptors prompted the scientific community to design ligands displaying either agonist and antagonist activity at the three main neurokinin receptors, called NK1, NK2 and NK3. Several strategies were implemented for this purpose. With a preference to small non-peptidic ligands, many research groups invested efforts in synthesizing and evaluating a wide range of scaffolds, but only the NK1 antagonist Aprepitant (EMENDT) and its prodrug Fosaprepitant (IVEMENDT) have been approved by the Food Drug Administration (FDA) for the treatment of Chemotherapy-Induced and Post-Operative Nausea and Vomiting (CINV and PONV, respectively). While non-peptidic drugs showed limitations, especially in side effect control, peptidic and pseudopeptidic compounds progressively regained attention. Various strategies were implemented to modulate affinity, selectivity and activity of the newly designed ligands. Replacement of canonical amino acids, incorporation of conformational constraints, and fusion with non-peptidic moieties gave rise to families of ligands displaying individual or dual NK1, NK2 and NK3 antagonism, that ultimately were combined with non-neurokinin ligands (such as opioids) to target enhanced biological impact.

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