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Journal of Inherited Metabolic Disease Nov 2023The Urea Cycle Disorders Consortium (UCDC) and the European registry and network for Intoxication type Metabolic Diseases (E-IMD) are the worldwide largest databases for... (Review)
Review
The Urea Cycle Disorders Consortium (UCDC) and the European registry and network for Intoxication type Metabolic Diseases (E-IMD) are the worldwide largest databases for individuals with urea cycle disorders (UCDs) comprising longitudinal data from more than 1100 individuals with an overall long-term follow-up of approximately 25 years. However, heterogeneity of the clinical phenotype as well as different diagnostic and therapeutic strategies hamper our understanding on the predictors of phenotypic diversity and the impact of disease-immanent and interventional variables (e.g., diagnostic and therapeutic interventions) on the long-term outcome. A new strategy using combined and comparative data analyses helped overcome this challenge. This review presents the mechanisms and relevant principles that are necessary for the identification of meaningful clinical associations by combining data from different data sources, and serves as a blueprint for future analyses of rare disease registries.
Topics: Humans; Urea Cycle Disorders, Inborn; Metabolic Diseases; Rare Diseases; Registries; Phenotype
PubMed: 37702610
DOI: 10.1002/jimd.12678 -
FASEB Journal : Official Publication of... Aug 2023Metabolic diseases are considered the primary culprit for physical and mental health of individuals. Although the diagnosis of these diseases is relatively easy, more... (Review)
Review
Metabolic diseases are considered the primary culprit for physical and mental health of individuals. Although the diagnosis of these diseases is relatively easy, more effective and convenient potent drugs are still being explored. Ca across the inner mitochondrial membrane is a vital intracellular messenger that regulates energy metabolism and cellular Ca homeostasis and is involved in cell death. Mitochondria rely on a selective mitochondrial Ca unidirectional transport complex (MCU complex) in their inner membrane for Ca uptake. We found that the channel contains several subunits and undergoes dramatic transformations in various pathological processes, especially in metabolic diseases. In this way, we believe that the MCU complex becomes a target with significant potential for these diseases. However, there is no review linking the two factors, thus hindering the possibility of new drug production. Here, we highlight the connection between MCU complex-related Ca transport and the pathophysiology of metabolic diseases, adding understanding and insight at the molecular level to provide new insights for targeting MCU to reverse metabolism-related diseases.
Topics: Humans; Mitochondria; Biological Transport; Cell Death; Energy Metabolism; Metabolic Diseases
PubMed: 37389546
DOI: 10.1096/fj.202300218R -
Experimental & Molecular Medicine Aug 2023Regenerating family member gamma, Reg3γ (the mouse homolog of human REG3A), belonging to the antimicrobial peptides (AMPs), functions as a part of the host immune... (Review)
Review
Regenerating family member gamma, Reg3γ (the mouse homolog of human REG3A), belonging to the antimicrobial peptides (AMPs), functions as a part of the host immune system to maintain spatial segregation between the gut bacteria and the host in the intestine via bactericidal activity. There is emerging evidence that gut manipulations such as bariatric surgery, dietary supplementation or drug treatment to produce metabolic benefits alter the gut microbiome. In addition to changes in a wide range of gut hormones, these gut manipulations also induce the expression of Reg3γ in the intestine. Studies over the past decades have revealed that Reg3γ not only plays a role in the gut lumen but can also contribute to host physiology through interaction with the gut microbiota. Herein, we discuss the current knowledge regarding the biology of Reg3γ, its role in various metabolic functions, and new opportunities for therapeutic strategies to treat metabolic disorders.
Topics: Animals; Mice; Bacteria; Gastrointestinal Microbiome; Metabolic Diseases; Pancreatitis-Associated Proteins
PubMed: 37524871
DOI: 10.1038/s12276-023-01054-5 -
Frontiers in Endocrinology 2024The topic of human circadian rhythms is not only attracting the attention of clinical researchers from various fields but also sparking a growing public interest. The... (Review)
Review
The topic of human circadian rhythms is not only attracting the attention of clinical researchers from various fields but also sparking a growing public interest. The circadian system comprises the central clock, located in the suprachiasmatic nucleus of the hypothalamus, and the peripheral clocks in various tissues that are interconnected; together they coordinate many daily activities, including sleep and wakefulness, physical activity, food intake, glucose sensitivity and cardiovascular functions. Disruption of circadian regulation seems to be associated with metabolic disorders (particularly impaired glucose tolerance) and cardiovascular disease. Previous clinical trials revealed that disturbance of the circadian system, specifically due to shift work, is associated with an increased risk of type 2 diabetes mellitus. This review is intended to provide clinicians who wish to implement knowledge of circadian disruption in diagnosis and strategies to avoid cardio-metabolic disease with a general overview of this topic.
Topics: Humans; Circadian Rhythm; Cardiovascular Diseases; Metabolic Diseases; Diabetes Mellitus, Type 2; Chronobiology Disorders
PubMed: 38742195
DOI: 10.3389/fendo.2024.1328139 -
Ageing Research Reviews Nov 2023The benefits of regular physical activity are related to delaying and reversing the onset of ageing and age-related disorders, including cardiomyopathy,... (Review)
Review
The benefits of regular physical activity are related to delaying and reversing the onset of ageing and age-related disorders, including cardiomyopathy, neurodegenerative diseases, cancer, obesity, diabetes, and fatty liver diseases. However, the molecular mechanisms of the benefits of exercise or physical activity on ageing and age-related disorders remain poorly understood. Mitochondrial dysfunction is implicated in the pathogenesis of ageing and age-related metabolic diseases. Mitochondrial health is an important mediator of cellular function. Therefore, exercise alleviates metabolic diseases in individuals with advancing ageing and age-related diseases by the remarkable promotion of mitochondrial biogenesis and function. Exerkines are identified as signaling moieties released in response to exercise. Exerkines released by exercise have potential roles in improving mitochondrial dysfunction in response to age-related disorders. This review comprehensive summarizes the benefits of exercise in metabolic diseases, linking mitochondrial dysfunction to the onset of age-related diseases. Using relevant examples utilizing this approach, the possibility of designing therapeutic interventions based on these molecular mechanisms is addressed.
Topics: Humans; Exercise; Metabolic Diseases; Mitochondria; Aging; Signal Transduction
PubMed: 37832607
DOI: 10.1016/j.arr.2023.102087 -
Internal and Emergency Medicine Oct 2023About 20% of adults worldwide have gallstones which are solid conglomerates in the biliary tree made of cholesterol monohydrate crystals, mucin, calcium bilirubinate,... (Review)
Review
About 20% of adults worldwide have gallstones which are solid conglomerates in the biliary tree made of cholesterol monohydrate crystals, mucin, calcium bilirubinate, and protein aggregates. About 20% of gallstone patients will definitively develop gallstone disease, a condition which consists of gallstone-related symptoms and/or complications requiring medical therapy, endoscopic procedures, and/or cholecystectomy. Gallstones represent one of the most prevalent digestive disorders in Western countries and patients with gallstone disease are one of the largest categories admitted to European hospitals. About 80% of gallstones in Western countries are made of cholesterol due to disturbed cholesterol homeostasis which involves the liver, the gallbladder and the intestine on a genetic background. The incidence of cholesterol gallstones is dramatically increasing in parallel with the global epidemic of insulin resistance, type 2 diabetes, expansion of visceral adiposity, obesity, and metabolic syndrome. In this context, gallstones can be largely considered a metabolic dysfunction-associated gallstone disease, a condition prone to specific and systemic preventive measures. In this review we discuss the key pathogenic and clinical aspects of gallstones, as the main clinical consequences of metabolic dysfunction-associated disease.
Topics: Adult; Humans; Gallstones; Diabetes Mellitus, Type 2; Liver; Metabolic Diseases; Cholesterol
PubMed: 37455265
DOI: 10.1007/s11739-023-03355-z -
Placenta Sep 2023The alarming increase in the prevalence of metabolic pathologies is of worldwide concern and has been linked not only to genetic factors but also to a large number of... (Review)
Review
The alarming increase in the prevalence of metabolic pathologies is of worldwide concern and has been linked not only to genetic factors but also to a large number of non-genetic factors. In recent years, there has been increasing interest in the study of the programming of metabolic diseases, such as type 2 diabetes mellitus (T2DM) and obesity, by paternal exposure, a paradigm termed "Paternal Origins of Health and Disease" (POHaD). This term derives from the better known "Developmental Origins of Health and Disease" (DOHaD), which focuses on the involvement of the maternal intrauterine environment and complications during pregnancy associated with the health and disease of the offspring. Studies on paternal programming have documented environmentally induced epigenetic modifications in the male germline and in seminal plasma, which lead to intergenerational and transgenerational phenotypes, evident already during fetoplacental development. Studies with animal models at both ends of the nutritional spectrum (undernutrition or overnutrition) have been performed to understand the possible mechanisms and signaling pathways leading to the programming of metabolic disorders by exploring epigenetic changes throughout the life of the offspring. The aim of this review was to address the evidence of the programming of fetoplacental developmental alterations and metabolic pathologies in the offspring of males with metabolic disorders and unhealthy exposures, highlighting the mechanisms involved in such programming and looking for paternal interventions to reduce negative health outcomes in the offspring.
Topics: Pregnancy; Male; Humans; Animals; Female; Diabetes Mellitus, Type 2; Metabolic Diseases; Epigenesis, Genetic; Obesity; Fathers
PubMed: 37355440
DOI: 10.1016/j.placenta.2023.06.009 -
Orphanet Journal of Rare Diseases Oct 2023Congenital disorders of glycosylation (CDG) are a complex and heterogeneous family of rare metabolic diseases. With a clinical history that dates back over 40 years, it... (Review)
Review
Congenital disorders of glycosylation (CDG) are a complex and heterogeneous family of rare metabolic diseases. With a clinical history that dates back over 40 years, it was the recent multi-omics advances that mainly contributed to the fast-paced and encouraging developments in the field. However, much remains to be understood, with targeted therapies' discovery and approval being the most urgent unmet need. In this paper, we present the 2022 state of the art of CDG, including glycosylation pathways, phenotypes, genotypes, inheritance patterns, biomarkers, disease models, and treatments. In light of our current knowledge, it is not always clear whether a specific disease should be classified as a CDG. This can create ambiguity among professionals leading to confusion and misguidance, consequently affecting the patients and their families. This review aims to provide the CDG community with a comprehensive overview of the recent progress made in this field.
Topics: Humans; Congenital Disorders of Glycosylation; Glycosylation; Biomarkers; Phenotype; Genotype
PubMed: 37858231
DOI: 10.1186/s13023-023-02879-z -
Biomedicine & Pharmacotherapy =... Jul 2024Pyroptosis is a lytic and pro-inflammatory form of regulated cell death characterized by the formation of membrane pores mediated by the gasdermin protein family. Two... (Review)
Review
Pyroptosis is a lytic and pro-inflammatory form of regulated cell death characterized by the formation of membrane pores mediated by the gasdermin protein family. Two main activation pathways have been documented: the caspase-1-dependent canonical pathway and the caspase-4/5/11-dependent noncanonical pathway. Pyroptosis leads to cell swelling, lysis, and the subsequent release of inflammatory mediators, including interleukin-1β (IL-1β) and interleukin-18 (IL-18). Chronic inflammation is a well-established foundation and driver for the development of metabolic diseases. Conversely, metabolic pathway dysregulation can also induce cellular pyroptosis. Recent studies have highlighted the significant role of pyroptosis modulation in various metabolic diseases, including type 2 diabetes mellitus, obesity, and metabolic (dysfunction) associated fatty liver disease. These findings suggest that pyroptosis may serve as a promising novel therapeutic target for metabolic diseases. This paper reviews an in-depth study of the current advancements in understanding the role of pyroptosis in the progression of metabolic diseases.
Topics: Pyroptosis; Humans; Metabolic Diseases; Animals; Signal Transduction; Inflammation
PubMed: 38850650
DOI: 10.1016/j.biopha.2024.116863 -
Frontiers in Endocrinology 2023
Topics: Humans; Wnt Signaling Pathway; Metabolic Diseases
PubMed: 37608791
DOI: 10.3389/fendo.2023.1254977