Perinatal programming of metabolic diseases: The role of glucocorticoids

: Emerging evidence supports an intertwining framework for the involvement of different inflammatory pathways in a common pathological background for a number of disorders. Of importance are pathways involving arachidonic acid metabolism by cyclooxygenase-2 (COX-2) and 15-lipoxygenase (15-LOX). Both enzyme activities and their products are implicated in a range of pathophysiological processes encompassing metabolic impairment leading to adipose inflammation and the subsequent vascular and neurological disorders, in addition to various pro-and anti-tumorigenic effects. A further layer of complexity is encountered by the disparate, and often reciprocal, modulatory effect COX-2 and 15-LOX activities and metabolites exert on each other or on other cellular targets, the most prominent of which is peroxisome proliferator-activated receptor gamma (PPARγ). Thus, effective therapeutic intervention with such multifaceted disorders requires the simultaneous modulation of more than one target. Here, we describe the role of COX-2, 15-LOX, and PPARγ in cancer and complications of metabolic disorders, highlight the value of designing multi-target directed ligands (MTDLs) modifying their activity, and summarize the available literature regarding the rationale and feasibility of design and synthesis of these ligands together with their known biological effects. We speculate on the potential impact of MTDLs in these disorders as well as emphasize the need for structured future effort to translate these early results facilitating the adoption of these, and similar, molecules in clinical research.

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Non-pharmacological Strategies Against Systemic Inflammation: Molecular Basis and Clinical Evidence

Current Pharmaceutical Design ◽

10.2174/1381612826666200403122600 ◽

2020 ◽

Vol 26 (22) ◽

pp. 2620-2629 ◽

Cited By ~ 2

Author(s):

Rita Del Pinto ◽

Davide Pietropaoli ◽

Annalisa Monaco ◽

Giovambattista Desideri ◽

Claudio Ferri ◽

...

Keyword(s):

Human Genome ◽

Systemic Inflammation ◽

Clinical Evidence ◽

Metabolic Diseases ◽

Lifestyle Changes ◽

Common Denominator ◽

Active Lifestyle ◽

Systemic Impact ◽

Public Health Strategies

Systemic inflammation is a common denominator to a variety of cardiovascular (CV) and non-CV diseases and relative risk factors, including hypertension and its control, metabolic diseases, rheumatic disorders, and those affecting the gastrointestinal tract. Besides medications, a non-pharmacological approach encompassing lifestyle changes and other complementary measures is mentioned in several updated guidelines on the management of these conditions. We performed an updated narrative review on the mechanisms behind the systemic impact of inflammation and the role of non-pharmacological, complementary measures centered on lowering systemic phlogosis for preserving or restoring a good global health. The central role of genetics in shaping the immune response is discussed in conjunction with that of the microbiome, highlighting the interdependence and mutual influences between the human genome and microbial integrity, diversity, and functions. Several plausible strategies to modulate inflammation and restore balanced crosstalk between the human genome and the microbiome are then recapitulated, including dietary measures, active lifestyle, and other potential approaches to manipulate the resident microbial community. To date, evidence from high-quality human studies is sparse to allow the unconditioned inclusion of understudied, though plausible solutions against inflammation into public health strategies for global wellness. This gap claims further focused, well-designed research targeted at unravelling the mechanisms behind future personalized medicine.

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Diet and Nutritional Interventions with the Special Role of Myo-Inositol in Gestational Diabetes Mellitus Management. An Evidence-Based Critical Appraisal

Current Pharmaceutical Design ◽

10.2174/1381612825666190722155512 ◽

2019 ◽

Vol 25 (22) ◽

pp. 2467-2473 ◽

Cited By ~ 1

Author(s):

Enrique Reyes-Muñoz ◽

Federica Di Guardo ◽

Michal Ciebiera ◽

Ilker Kahramanoglu ◽

Thozhukat Sathyapalan ◽

...

Keyword(s):

Diabetes Mellitus ◽

Gestational Diabetes ◽

Gestational Diabetes Mellitus ◽

Metabolic Diseases ◽

Nutritional Intervention ◽

Attractive Alternative ◽

Special Role ◽

Dose Frequency ◽

Nutritional Interventions

Background: Gestational Diabetes Mellitus (GDM), defined as glucose intolerance with onset or first recognition during pregnancy, represents one of the most common maternal-fetal complications during pregnancy and it is associated with poor perinatal outcomes. To date, GDM is a rising condition over the last decades coinciding with the ongoing epidemic of obesity and Type 2 Diabetes Mellitus (T2DM). Objective: The aim of this review is to discuss the role of diet and nutritional interventions in preventing GDM with the explanation of the special role of myo-inositol (MI) in this matter. Methods: We performed an overview of the most recent literature data on the subject with particular attention to the effectiveness of diet and nutritional interventions in the prevention of GDM with the special role of MI. Results: Nutritional intervention and physical activity before and during pregnancy are mandatory in women affected by GDM. Moreover, the availability of insulin-sensitizers such as different forms of inositol has dramatically changed the scenario, allowing the treatment of several metabolic diseases, such as those related to glucose dysbalance. Although the optimal dose, frequency, and form of MI administration need to be further investigated, diet supplementation with MI appears to be an attractive alternative for the GDM prevention as well as for the reduction of GDM-related complications. Conclusion: More studies should be conducted to prove the most effective nutritional intervention in GDM. Regarding the potential effectiveness of MI, further evidence in multicenter, randomized controlled trials is needed to draw firm conclusions.

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Role of Exosomes in the Exchange of Spermatozoa after Leaving the Seminiferous Tubule: A Review

Current Drug Metabolism ◽

10.2174/1389200221666200520091511 ◽

2020 ◽

Vol 21 (5) ◽

pp. 330-338

Author(s):

Luming Wu ◽

Yuan Ding ◽

Shiqiang Han ◽

Yiqing Wang

Keyword(s):

Drug Delivery ◽

Plasma Membrane ◽

Seminiferous Tubule ◽

Metabolic Diseases ◽

Inflammatory Diseases ◽

Multivesicular Bodies ◽

Extensive Search ◽

Neurological Research ◽

The One

Background: Exosomes are extracellular vesicles (EVs) released from cells upon fusion of an intermediate endocytic compartment with the plasma membrane. They refer to the intraluminal vesicles released from the fusion of multivesicular bodies with the plasma membrane. The contents and number of exosomes are related to diseases such as metabolic diseases, cancer and inflammatory diseases. Exosomes have been used in neurological research as a drug delivery tool and also as biomarkers for diseases. Recently, exosomes were observed in the seminal plasma of the one who is asthenozoospermia, which can affect sperm motility and capacitation. Objective: The main objective of this review is to deeply discuss the role of exosomes in spermatozoa after leaving the seminiferous tubule. Methods: We conducted an extensive search of the literature available on relationships between exosomes and exosomes in spermatozoa on the bibliographic database. Conclusion: : This review thoroughly discussed the role that exosomes play in the exchange of spermatozoa after leaving the seminiferous tubule and its potential as a drug delivery tool and biomarkers for diseases as well.

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The Role of Neuropeptide Y and Peptide YY in the Development of Obesity via Gut-brain Axis

Current Protein and Peptide Science ◽

10.2174/1389203720666190125105401 ◽

2019 ◽

Vol 20 (7) ◽

pp. 750-758 ◽

Cited By ~ 7

Author(s):

Yi Wu ◽

Hengxun He ◽

Zhibin Cheng ◽

Yueyu Bai ◽

Xi Ma

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Neuropeptide Y ◽

Metabolic Diseases ◽

Peptide Yy ◽

Vital Role ◽

Gut Peptides ◽

Nonalcoholic Fatty Liver ◽

The Central Nervous System

Obesity is one of the main challenges of public health in the 21st century. Obesity can induce a series of chronic metabolic diseases, such as diabetes, dyslipidemia, hypertension and nonalcoholic fatty liver, which seriously affect human health. Gut-brain axis, the two-direction pathway formed between enteric nervous system and central nervous system, plays a vital role in the occurrence and development of obesity. Gastrointestinal signals are projected through the gut-brain axis to nervous system, and respond to various gastrointestinal stimulation. The central nervous system regulates visceral activity through the gut-brain axis. Brain-gut peptides have important regulatory roles in the gut-brain axis. The brain-gut peptides of the gastrointestinal system and the nervous system regulate the gastrointestinal movement, feeling, secretion, absorption and other complex functions through endocrine, neurosecretion and paracrine to secrete peptides. Both neuropeptide Y and peptide YY belong to the pancreatic polypeptide family and are important brain-gut peptides. Neuropeptide Y and peptide YY have functions that are closely related to appetite regulation and obesity formation. This review describes the role of the gutbrain axis in regulating appetite and maintaining energy balance, and the functions of brain-gut peptides neuropeptide Y and peptide YY in obesity. The relationship between NPY and PYY and the interaction between the NPY-PYY signaling with the gut microbiota are also described in this review.

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Covid-19 In Man: A Very Dangerous Affair.

Endocrine Metabolic & Immune Disorders - Drug Targets ◽

10.2174/1871530321666210101123801 ◽

2021 ◽

Vol 21 ◽

Author(s):

Giuseppe Lisco ◽

Vito A. Giagulli ◽

Giovanni De Pergola ◽

Anna De Tullio ◽

Edoardo Guastamacchia ◽

...

Keyword(s):

Poor Prognosis ◽

Metabolic Diseases ◽

Systemic Disease ◽

Public Health Issue ◽

Immune System Dysfunction ◽

Data Support ◽

Systemic Spread ◽

The Impact

Background: The novel pandemic of Coronavirus disease 2019 (COVID-19) has becoming a public health issue since March 2020 considering that more than 30 million people were found to be infected worldwide. Particularly, recent evidences suggested that men may be considered as at higher risk of poor prognosis or death once the infection occurred and concerns surfaced in regard of the risk of a possible testicular injury due to SARS-CoV-2 infection. Results: Several data support the existence of a bivalent role of testosterone (T) in driving poor prognosis in patients with COVID-19. On one hand, this is attributable to the fact that T may facilitate SARS-CoV-2 entry in human cells by means of an enhanced expression of transmembrane serine-protease 2 (TMPRSS2) and angiotensin-converting enzyme 2 (ACE2). At the same time, younger man with normal testicular function compared to women of similar age are prone to develop a blunted immune response against SARS-CoV-2, being exposed to less viral clearance and more viral shedding and systemic spread of the disease. Conversely, low levels of serum T observed in hypogonadal men predispose them to a greater background systemic inflammation, cardiovascular and metabolic diseases, and immune system dysfunction, hence driving harmful consequences once SARS-CoV-2 infection occurred. Finally, SARS-CoV-2, as a systemic disease, may also affect testicles with possible concerns for current and future testicular efficiency. Preliminary data suggested that SARS-CoV-2 genome is not normally found in gonads and gametes, therefore sex transmission could be excluded as a possible way to spread the COVID-19. Conclusion: Most data support a role of T as a bivalent risk factor for poor prognosis (high/normal in younger; lower in elderly) in COVID-19. However, the impact of medical treatment aimed to modify T homeostasis for improving the prognosis of affected patients is unknown in this clinical setting. In addition, testicular damage may be a harmful consequence of the infection even in case it occurred asymptomatically but no long-term evidences are currently available to confirm and quantify this phenomenon. Different authors excluded the presence of SARS-CoV-2 in sperm and oocytes, thus limiting worries about both a potential sexual and gamete-to-embryos transmission of COVID-19. Despite these evidence, long-term and well-designed studies are needed to clarify these issues.

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Fructose and Mannose in Inborn Errors of Metabolism and Cancer

Metabolites ◽

10.3390/metabo11080479 ◽

2021 ◽

Vol 11 (8) ◽

pp. 479

Author(s):

Elizabeth L. Lieu ◽

Neil Kelekar ◽

Pratibha Bhalla ◽

Jiyeon Kim

Keyword(s):

Metabolic Disease ◽

Inborn Errors Of Metabolism ◽

Metabolic Diseases ◽

Treatment Options ◽

Biochemical Properties ◽

Biological Molecules ◽

Diagnostic Tools ◽

Inborn Errors ◽

Mannose Metabolism

History suggests that tasteful properties of sugar have been domesticated as far back as 8000 BCE. With origins in New Guinea, the cultivation of sugar quickly spread over centuries of conquest and trade. The product, which quickly integrated into common foods and onto kitchen tables, is sucrose, which is made up of glucose and fructose dimers. While sugar is commonly associated with flavor, there is a myriad of biochemical properties that explain how sugars as biological molecules function in physiological contexts. Substantial research and reviews have been done on the role of glucose in disease. This review aims to describe the role of its isomers, fructose and mannose, in the context of inborn errors of metabolism and other metabolic diseases, such as cancer. While structurally similar, fructose and mannose give rise to very differing biochemical properties and understanding these differences will guide the development of more effective therapies for metabolic disease. We will discuss pathophysiology linked to perturbations in fructose and mannose metabolism, diagnostic tools, and treatment options of the diseases.

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Role of small leucine zipper protein in hepatic gluconeogenesis and metabolic disorder

Journal of Molecular Cell Biology ◽

10.1093/jmcb/mjaa069 ◽

2020 ◽

Author(s):

Minsoo Kang ◽

Sun Kyoung Han ◽

Suhyun Kim ◽

Sungyeon Park ◽

Yerin Jo ◽

...

Keyword(s):

Blood Glucose ◽

Glucose Metabolism ◽

Metabolic Disorder ◽

Leucine Zipper ◽

Metabolic Diseases ◽

Adenosine Monophosphate ◽

The Body ◽

Hepatic Gluconeogenesis ◽

Leucine Zipper Protein

Abstract Hepatic gluconeogenesis is the central pathway for glucose generation in the body. The imbalance between glucose synthesis and uptake leads to metabolic diseases such as obesity, diabetes, and cardiovascular diseases. Small leucine zipper protein (sLZIP) is an isoform of LZIP and it mainly functions as a transcription factor. Although sLZIP is known to regulate the transcription of genes involved in various cellular processes, the role of sLZIP in hepatic glucose metabolism is not known. In this study, we investigated the regulatory role of sLZIP in hepatic gluconeogenesis and its involvement in metabolic disorder. We found that sLZIP expression was elevated during glucose starvation, leading to the promotion of phosphoenolpyruvate carboxylase and glucose-6-phosphatase expression in hepatocytes. However, sLZIP knockdown suppressed the expression of the gluconeogenic enzymes under low glucose conditions. sLZIP also enhanced glucose production in the human liver cells and mouse primary hepatic cells. Fasting-induced cyclic adenosine monophosphate impeded sLZIP degradation. Results of glucose and pyruvate tolerance tests showed that sLZIP transgenic mice exhibited abnormal blood glucose metabolism. These findings suggest that sLZIP is a novel regulator of gluconeogenic enzyme expression and plays a role in blood glucose homeostasis during starvation.

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Immune-endocrine interactions related to a high risk of infections in chronic metabolic diseases: The role of PPAR gamma

European Journal of Pharmacology ◽

10.1016/j.ejphar.2019.04.008 ◽

2019 ◽

Vol 854 ◽

pp. 272-281 ◽

Cited By ~ 6

Author(s):

Adriana Ribeiro Silva ◽

Cassiano Felippe Gonçalves-de-Albuquerque ◽

Ana Rosa Pérez ◽

Vinicius de Frias Carvalho

Keyword(s):

High Risk ◽

Metabolic Diseases ◽

Ppar Gamma

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